Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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8 pages, 2264 KiB  
Article
Radical Prostatectomy without Prior Biopsy in Patients with High Suspicion of Prostate Cancer Based on Multiparametric Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen Positron Emission Tomography: A Prospective Cohort Study
by Michael Chaloupka, Maria Apfelbeck, Nikolaos Pyrgidis, Julian Marcon, Philipp Weinhold and Christian G. Stief
Cancers 2023, 15(4), 1266; https://doi.org/10.3390/cancers15041266 - 16 Feb 2023
Cited by 7 | Viewed by 1469
Abstract
Modern risk stratification of prostate cancer (PCa) allows for prediction of advanced disease with a high level of certainty. We aimed to evaluate a prospective series of patients undergoing radical prostatectomy without prior biopsy based solely on clinical criteria and imaging results. The [...] Read more.
Modern risk stratification of prostate cancer (PCa) allows for prediction of advanced disease with a high level of certainty. We aimed to evaluate a prospective series of patients undergoing radical prostatectomy without prior biopsy based solely on clinical criteria and imaging results. The patients were divided into three groups. Group 1 included 27 patients with: (i) suspicious digital rectal examination, (ii) PSA ≥ 10 ng/mL, (iii) PI-RADS 4/5 on mpMRI, and (iv) high suspicion of PCa on PSMA-PET. Group 2 included six patients who fulfilled criteria i, ii, and iii but did not undergo PSMA-PET imaging. Group 3 included 17 patients with at least one clinical (i or ii) and one imaging (iii or iv) criterion. All of the patients were diagnosed with PCa. Comparison of Group 1 and 2 versus Group 3 showed a significantly higher ratio of locally advanced PCa for Groups 1 and 2 compared to Group 3 (60.6% versus 11.8%, p = 0.005, respectively). Similarly, these patients displayed a significantly higher ratio of aggressive PCa (ISUP grade > 2: 66.7% versus 23.5%, p = 0.027, respectively) and tumor infiltration (median tumor infiltration: 32.5% vs. 15%, p = 0.001, respectively) in the final specimen compared to Group 3. In conclusion, we have shown that radical prostatectomy without prior biopsy is safe in terms of the diagnosis of clinically significant PCa when proper preoperative risk stratification involving mpMRI and PSMA-PET imaging is applied. Full article
(This article belongs to the Section Cancer Therapy)
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21 pages, 2645 KiB  
Review
NKG2A Immune Checkpoint in Vδ2 T Cells: Emerging Application in Cancer Immunotherapy
by Valentina Cazzetta, Delphine Depierreux, Francesco Colucci, Joanna Mikulak and Domenico Mavilio
Cancers 2023, 15(4), 1264; https://doi.org/10.3390/cancers15041264 - 16 Feb 2023
Cited by 3 | Viewed by 2824
Abstract
Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the [...] Read more.
Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the immune environment of the cancer cells. Current challenges associated with the enhancement of ICI effects are increasing the fraction of responding patients through personalized combinations of multiple ICIs and overcoming acquired resistance. This requires a complete overview of the anti-tumor immune response, which depends on a complex interplay between innate and adaptive immune cells with the tumor microenvironment. The NKG2A was revealed to be a key immune checkpoint for both Natural Killer (NK) cells and T cells. Monalizumab, a humanized anti-NKG2A antibody, enhances NK cell activity against various tumor cells and rescues CD8 αβ T cell function in combination with PD-1/PD-L1 blockade. In this review, we discuss the potential for targeting NKG2A expressed on tumor-sensing human γδ T cells, mostly on the specific Vδ2 T cell subset, in order to emphasize its importance and potential in the development of new ICI-based therapeutic approaches. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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12 pages, 862 KiB  
Review
CAR-T Therapy in GBM: Current Challenges and Avenues for Improvement
by Ayush Pant and Michael Lim
Cancers 2023, 15(4), 1249; https://doi.org/10.3390/cancers15041249 - 16 Feb 2023
Cited by 7 | Viewed by 2574
Abstract
Completed clinical trials of CAR-T cells in glioblastoma (GBM) have revealed key challenges that limit their efficacy. These include incomplete antigen coverage, downregulation of target antigen in response to therapy, exposure to immunosuppressive cells and cytokines in the tumor microenvironment and exhaustion of [...] Read more.
Completed clinical trials of CAR-T cells in glioblastoma (GBM) have revealed key challenges that limit their efficacy. These include incomplete antigen coverage, downregulation of target antigen in response to therapy, exposure to immunosuppressive cells and cytokines in the tumor microenvironment and exhaustion of CAR-T cells. To overcome these challenges, CAR-T cells have been modified to maximize effector function and resist immunosuppression in the tumor while limiting toxicities to the host. Adoption of these novel CAR-T strategies in GBM can overcome the “cold tumor” phenotype of GBM and trigger an inflammatory cascade that maximizes tumor clearance and minimizes CAR-T dysfunction. To achieve this, understanding and harnessing the antigenic, metabolic and immunological composition of GBM is crucial. Here we review the findings from completed clinical trials of CAR-T cells in GBM as well as novel strategies that could improve CAR-T survival and function in the tumor. Full article
(This article belongs to the Collection Treatment of Glioma)
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28 pages, 1165 KiB  
Review
Hypoxia, a Targetable Culprit to Counter Pancreatic Cancer Resistance to Therapy
by Raefa Abou Khouzam, Jean-Marie Lehn, Hemma Mayr, Pierre-Alain Clavien, Michael Bradley Wallace, Michel Ducreux, Perparim Limani and Salem Chouaib
Cancers 2023, 15(4), 1235; https://doi.org/10.3390/cancers15041235 - 15 Feb 2023
Cited by 8 | Viewed by 2478
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it is a disease of dismal prognosis. While immunotherapy has revolutionized the treatment of various solid tumors, it has achieved little success in PDAC. Hypoxia within the stroma-rich tumor microenvironment [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it is a disease of dismal prognosis. While immunotherapy has revolutionized the treatment of various solid tumors, it has achieved little success in PDAC. Hypoxia within the stroma-rich tumor microenvironment is associated with resistance to therapies and promotes angiogenesis, giving rise to a chaotic and leaky vasculature that is inefficient at shuttling oxygen and nutrients. Hypoxia and its downstream effectors have been implicated in immune resistance and could be contributing to the lack of response to immunotherapy experienced by patients with PDAC. Paradoxically, increasing evidence has shown hypoxia to augment genomic instability and mutagenesis in cancer, suggesting that hypoxic tumor cells could have increased production of neoantigens that can potentially enable their clearance by cytotoxic immune cells. Strategies aimed at relieving this condition have been on the rise, and one such approach opts for normalizing the tumor vasculature to reverse hypoxia and its downstream support of tumor pathogenesis. An important consideration for the successful implementation of such strategies in the clinic is that not all PDACs are equally hypoxic, therefore hypoxia-detection approaches should be integrated to enable optimal patient selection for achieving improved patient outcomes. Full article
(This article belongs to the Collection Recent Advances in Pancreatic Ductal Adenocarcinoma)
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25 pages, 775 KiB  
Review
Radiomics Applications in Head and Neck Tumor Imaging: A Narrative Review
by Mario Tortora, Laura Gemini, Alessandra Scaravilli, Lorenzo Ugga, Andrea Ponsiglione, Arnaldo Stanzione, Felice D’Arco, Gennaro D’Anna and Renato Cuocolo
Cancers 2023, 15(4), 1174; https://doi.org/10.3390/cancers15041174 - 12 Feb 2023
Cited by 10 | Viewed by 2191
Abstract
Recent advances in machine learning and artificial intelligence technology have ensured automated evaluation of medical images. As a result, quantifiable diagnostic and prognostic biomarkers have been created. We discuss radiomics applications for the head and neck region in this paper. Molecular characterization, categorization, [...] Read more.
Recent advances in machine learning and artificial intelligence technology have ensured automated evaluation of medical images. As a result, quantifiable diagnostic and prognostic biomarkers have been created. We discuss radiomics applications for the head and neck region in this paper. Molecular characterization, categorization, prognosis and therapy recommendation are given special consideration. In a narrative manner, we outline the fundamental technological principles, the overall idea and usual workflow of radiomic analysis and what seem to be the present and potential challenges in normal clinical practice. Clinical oncology intends for all of this to ensure informed decision support for personalized and useful cancer treatment. Head and neck cancers present a unique set of diagnostic and therapeutic challenges. These challenges are brought on by the complicated anatomy and heterogeneity of the area under investigation. Radiomics has the potential to address these barriers. Future research must be interdisciplinary and focus on the study of certain oncologic functions and outcomes, with external validation and multi-institutional cooperation in order to achieve this. Full article
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27 pages, 471 KiB  
Review
CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets
by John Maher and David M. Davies
Cancers 2023, 15(4), 1171; https://doi.org/10.3390/cancers15041171 - 11 Feb 2023
Cited by 7 | Viewed by 5224
Abstract
Immunotherapy with CAR T-cells has revolutionised the treatment of B-cell and plasma cell-derived cancers. However, solid tumours present a much greater challenge for treatment using CAR-engineered immune cells. In a partner review, we have surveyed data generated in clinical trials in which patients [...] Read more.
Immunotherapy with CAR T-cells has revolutionised the treatment of B-cell and plasma cell-derived cancers. However, solid tumours present a much greater challenge for treatment using CAR-engineered immune cells. In a partner review, we have surveyed data generated in clinical trials in which patients with solid tumours that expressed any of 30 discrete targets were treated with CAR-based immunotherapy. That exercise confirms that efficacy of this approach falls well behind that seen in haematological malignancies, while significant toxic events have also been reported. Here, we consider approximately 60 additional candidates for which such clinical data are not available yet, but where pre-clinical data have provided support for their advancement to clinical evaluation as CAR target antigens. Full article
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31 pages, 1969 KiB  
Review
Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy
by Hafiza Padinharayil, Vikrant Rai and Alex George
Cancers 2023, 15(4), 1070; https://doi.org/10.3390/cancers15041070 - 08 Feb 2023
Cited by 5 | Viewed by 2507
Abstract
Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells’ [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells’ potential to produce ATP as energy, despite retaining the redox potential optimum, and allocating materials for biosynthetic activities that are crucial for cell growth, survival, and proliferation, are assisted by mitochondria. The polyclonal tumor cells with different metabolic profiles may add to carcinogenesis through inter-metabolic coupling. Cancer cells frequently possess alterations in the mitochondrial genome, although they do not hinder metabolism; alternatively, they change bioenergetics. This can further impart retrograde signaling, educate cell signaling, epigenetic modifications, chromatin structures, and transcription machinery, and ultimately satisfy cancer cellular and nuclear demands. To maximize the tumor microenvironment (TME), tumor cells remodel nearby stromal cells and extracellular matrix. These changes initiate polyclonality, which is crucial for growth, stress response, and metastasis. Here, we evaluate all the intrinsic and extrinsic pathways drawn by mitochondria in carcinogenesis, emphasizing the perspectives of mitochondrial metabolism in PDAC progression and treatment. Full article
(This article belongs to the Special Issue Mitochondria and Metabolism of Pancreatic Adenocarcinoma Cells)
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23 pages, 3095 KiB  
Review
Aquaporins and Ion Channels as Dual Targets in the Design of Novel Glioblastoma Therapeutics to Limit Invasiveness
by Alanah Varricchio and Andrea J. Yool
Cancers 2023, 15(3), 849; https://doi.org/10.3390/cancers15030849 - 30 Jan 2023
Cited by 1 | Viewed by 2855
Abstract
Current therapies for Glioblastoma multiforme (GBM) focus on eradicating primary tumors using radiotherapy, chemotherapy and surgical resection, but have limited success in controlling the invasive spread of glioma cells into a healthy brain, the major factor driving short survival times for patients post-diagnosis. [...] Read more.
Current therapies for Glioblastoma multiforme (GBM) focus on eradicating primary tumors using radiotherapy, chemotherapy and surgical resection, but have limited success in controlling the invasive spread of glioma cells into a healthy brain, the major factor driving short survival times for patients post-diagnosis. Transcriptomic analyses of GBM biopsies reveal clusters of membrane signaling proteins that in combination serve as robust prognostic indicators, including aquaporins and ion channels, which are upregulated in GBM and implicated in enhanced glioblastoma motility. Accumulating evidence supports our proposal that the concurrent pharmacological targeting of selected subclasses of aquaporins and ion channels could impede glioblastoma invasiveness by impairing key cellular motility pathways. Optimal sets of channels to be selected as targets for combined therapies could be tailored to the GBM cancer subtype, taking advantage of differences in patterns of expression between channels that are characteristic of GBM subtypes, as well as distinguishing them from non-cancerous brain cells such as neurons and glia. Focusing agents on a unique channel fingerprint in GBM would further allow combined agents to be administered at near threshold doses, potentially reducing off-target toxicity. Adjunct therapies which confine GBM tumors to their primary sites during clinical treatments would offer profound advantages for treatment efficacy. Full article
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44 pages, 1995 KiB  
Review
Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities
by Himani Pandey, Daryl W. T. Tang, Sunny H. Wong and Devi Lal
Cancers 2023, 15(3), 866; https://doi.org/10.3390/cancers15030866 - 30 Jan 2023
Cited by 14 | Viewed by 4790
Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer [...] Read more.
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer to the ~40 trillion microorganisms that inhabit the human gut. Advances in next-generation sequencing technologies and metagenomics have provided new insights into the gut microbial ecology and have helped in linking gut microbiota to CRC. Many studies carried out in humans and animal models have emphasized the role of certain gut bacteria, such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, in the onset and progression of CRC. Metagenomic studies have opened up new avenues for the application of gut microbiota in the diagnosis, prevention, and treatment of CRC. This review article summarizes the role of gut microbiota in CRC development and its use as a biomarker to predict the disease and its potential therapeutic applications. Full article
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13 pages, 1717 KiB  
Article
Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection
by Dmitri Pchejetski, Ewan Hunter, Mehrnoush Dezfouli, Matthew Salter, Ryan Powell, Jayne Green, Tarun Naithani, Christina Koutsothanasi, Heba Alshaker, Jiten Jaipuria, Martin J. Connor, David Eldred-Evans, Francesca Fiorentino, Hashim Ahmed, Alexandre Akoulitchev and Mathias Winkler
Cancers 2023, 15(3), 821; https://doi.org/10.3390/cancers15030821 - 29 Jan 2023
Cited by 2 | Viewed by 17111
Abstract
Background: Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of [...] Read more.
Background: Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of any prostate cancer, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with PCa. We have recently identified circulating chromosome conformation signatures (CCSs, Episwitch® PCa test) allowing PCa detection and risk stratification in line with standards of clinical PCa staging. The purpose of this study was to determine whether combining the Episwitch PCa test with the PSA test will increase its diagnostic accuracy. Methods: n = 109 whole blood samples of men enrolled in the PROSTAGRAM screening pilot study and n = 38 samples of patients with established PCa diagnosis and cancer-negative controls from Imperial College NHS Trust were used. Samples were tested for PSA, and the presence of CCSs in the loci encoding for of DAPK1, HSD3B2, SRD5A3, MMP1, and miRNA98 associated with high-risk PCa identified in our previous work. Results: PSA > 3 ng/mL alone showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. EpiSwitch alone showed a PPV of 0.91 and a NPV of 0.32. Combining PSA and Episwitch tests has significantly increased the PPV to 0.81 although reducing the NPV to 0.78. Furthermore, integrating PSA, as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, Prostate Screening EpiSwitch (PSE) test, has yielded a remarkable combined PPV of 0.93 and NPV of 0.95 when tested on the independent combined cohort. Conclusions: Our results demonstrate that combining the standard PSA readout with circulating chromosome conformations (PSE test) allows for significantly enhanced PSA PPV and overall accuracy for PCa detection. The PSE test is accurate, rapid, minimally invasive, and inexpensive, suggesting significant screening diagnostic potential to minimise unnecessary referrals for expensive and invasive MRI and/or biopsy testing. Further extended prospective blinded validation of the new combined signature in a screening cohort with low cancer prevalence would be the recommended step for PSE adoption in PCa screening. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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13 pages, 1181 KiB  
Review
CAR-T Cell Therapy and the Gut Microbiota
by Sahana Asokan, Nyssa Cullin, Christoph K. Stein-Thoeringer and Eran Elinav
Cancers 2023, 15(3), 794; https://doi.org/10.3390/cancers15030794 - 28 Jan 2023
Cited by 5 | Viewed by 4452
Abstract
Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the [...] Read more.
Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the cancer immunotherapy arsenal, more than half of patients receiving CAR-T infusions do not respond, while others develop significant adverse effects, collectively indicating a need for optimization of CAR-T treatment to the individual. The microbiota is increasingly suggested as a major modulator of immunotherapy responsiveness. Studying causal microbiota roles possibly contributing to CAR-T therapy efficacy, adverse effects reduction, and prediction of patient responsiveness constitutes an exciting area of active research. Herein, we discuss the latest developments implicating human microbiota involvement in CAR-T therapy, while highlighting challenges and promises in harnessing the microbiota as a predictor and modifier of CAR-T treatment towards optimized efficacy and minimization of treatment-related adverse effects. Full article
(This article belongs to the Special Issue CAR T-cell Therapy for Lymphoma Research)
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29 pages, 1727 KiB  
Review
Current Status and Future Prospects for Esophageal Cancer
by Mahdi Sheikh, Gholamreza Roshandel, Valerie McCormack and Reza Malekzadeh
Cancers 2023, 15(3), 765; https://doi.org/10.3390/cancers15030765 - 26 Jan 2023
Cited by 29 | Viewed by 4717
Abstract
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence [...] Read more.
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes. Full article
(This article belongs to the Special Issue Current Status and Future Prospects for Oesophageal Cancer)
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15 pages, 787 KiB  
Review
Tumor Infiltrating Lymphocytes across Breast Cancer Subtypes: Current Issues for Biomarker Assessment
by Carmine Valenza, Beatrice Taurelli Salimbeni, Celeste Santoro, Dario Trapani, Gabriele Antonarelli and Giuseppe Curigliano
Cancers 2023, 15(3), 767; https://doi.org/10.3390/cancers15030767 - 26 Jan 2023
Cited by 15 | Viewed by 2718
Abstract
Tumor-infiltrating lymphocytes (TILs) represent a surrogate biomarker of anti-tumor, lymphocyte-mediated immunity. In early, triple-negative breast cancer, TILs have level 1B of evidence to predict clinical outcomes. TILs represent a promising biomarker to select patients who can experience a better prognosis with de-intensified cancer [...] Read more.
Tumor-infiltrating lymphocytes (TILs) represent a surrogate biomarker of anti-tumor, lymphocyte-mediated immunity. In early, triple-negative breast cancer, TILs have level 1B of evidence to predict clinical outcomes. TILs represent a promising biomarker to select patients who can experience a better prognosis with de-intensified cancer treatments and derive larger benefits from immune checkpoint inhibitors. However, the assessment and the validation of TILs as a biomarker require a prospective and rigorous demonstration of its clinical validity and utility, provided reproducible analytical performance. With pending data about the prospective validation of TILs’ clinical validity to modulate treatments in early breast cancer, this review summarizes the most important current issues and future challenges related to the implementation of TILs assessments across all breast cancer subtypes and their potential integration into clinical practice. Full article
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31 pages, 974 KiB  
Review
Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy
by Marianna Sirico, Alberto D’Angelo, Caterina Gianni, Chiara Casadei, Filippo Merloni and Ugo De Giorgi
Cancers 2023, 15(3), 703; https://doi.org/10.3390/cancers15030703 - 23 Jan 2023
Cited by 11 | Viewed by 2579
Abstract
The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most [...] Read more.
The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice. Full article
(This article belongs to the Special Issue PI3K Pathway in Cancer)
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17 pages, 920 KiB  
Article
Safety and Feasibility of Radiation Therapy Combined with CDK 4/6 Inhibitors in the Management of Advanced Breast Cancer
by Marcin Kubeczko, Dorota Gabryś, Marzena Gawkowska, Anna Polakiewicz-Gilowska, Alexander J. Cortez, Aleksandra Krzywon, Grzegorz Woźniak, Tomasz Latusek, Aleksandra Leśniak, Katarzyna Świderska, Marta Mianowska-Malec, Barbara Łanoszka, Konstanty Chomik, Mateusz Gajek, Anna Michalik, Elżbieta Nowicka, Rafał Tarnawski, Tomasz Rutkowski and Michał Jarząb
Cancers 2023, 15(3), 690; https://doi.org/10.3390/cancers15030690 - 22 Jan 2023
Cited by 5 | Viewed by 3255
Abstract
The addition of CDK4/6 inhibitors to endocrine therapy in advanced hormone receptor-positive HER2-negative breast cancer has led to practice-changing improvements in overall survival. However, data concerning the safety of CDK4/6i combination with radiotherapy (RT) are conflicting. A retrospective evaluation of 288 advanced breast [...] Read more.
The addition of CDK4/6 inhibitors to endocrine therapy in advanced hormone receptor-positive HER2-negative breast cancer has led to practice-changing improvements in overall survival. However, data concerning the safety of CDK4/6i combination with radiotherapy (RT) are conflicting. A retrospective evaluation of 288 advanced breast cancer patients (pts) treated with CDK4/6i was performed, and 100 pts also received RT. Forty-six pts received 63 RT courses concurrently and fifty-four sequentially before CDK4/6i initiation (76 RT courses). Neutropenia was common (79%) and more frequent during and after concurrent RT than sequential RT (86% vs. 76%); however, CDK4/6i dose reduction rates were similar. In patients treated with CDK4/6i alone, the dose reduction rate was 42% (79 pts) versus 38% with combined therapy, and 5% discontinued treatment due to toxicity in the combined group. The risk of CDK4/6i dose reduction was correlated with neutropenia grade, RT performed within the first two CDK4/6i cycles, and more than one concurrent RT; a tendency was observed in concurrent bone irradiation. However, on multivariate regression analysis, only ECOG 1 performance status and severe neutropenia at the beginning of the second cycle were found to be associated with a higher risk of CDK4/6i dose reduction. This largest single-center experience published to date confirmed the acceptable safety profile of the CDK4/6i and RT combination without a significantly increased toxicity compared with CDK4/6i alone. However, one might delay RT for the first two CDK4/6i cycles, when myelotoxic AE are most common. Full article
(This article belongs to the Special Issue Radiation Therapy for Breast Cancer: Recent Advances and Challenges)
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25 pages, 1287 KiB  
Review
Treatment Strategies for Non-Small Cell Lung Cancer with Common EGFR Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data
by Julian A. Marin-Acevedo, Bruna Pellini, ErinMarie O. Kimbrough, J. Kevin Hicks and Alberto Chiappori
Cancers 2023, 15(3), 629; https://doi.org/10.3390/cancers15030629 - 19 Jan 2023
Cited by 7 | Viewed by 4361
Abstract
The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC [...] Read more.
The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations. Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
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22 pages, 2233 KiB  
Review
MicroRNAs in the Pathogenesis, Prognostication and Prediction of Treatment Resistance in Soft Tissue Sarcomas
by Andrea York Tiang Teo, Vivian Yujing Lim and Valerie Shiwen Yang
Cancers 2023, 15(3), 577; https://doi.org/10.3390/cancers15030577 - 18 Jan 2023
Viewed by 4162
Abstract
Soft tissue sarcomas are highly aggressive malignant neoplasms of mesenchymal origin, accounting for less than 1% of adult cancers, but comprising over 20% of paediatric solid tumours. In locally advanced, unresectable, or metastatic disease, outcomes from even the first line of systemic treatment [...] Read more.
Soft tissue sarcomas are highly aggressive malignant neoplasms of mesenchymal origin, accounting for less than 1% of adult cancers, but comprising over 20% of paediatric solid tumours. In locally advanced, unresectable, or metastatic disease, outcomes from even the first line of systemic treatment are invariably poor. MicroRNAs (miRNAs), which are short non-coding RNA molecules, target and modulate multiple dysregulated target genes and/or signalling pathways within cancer cells. Accordingly, miRNAs demonstrate great promise for their utility in diagnosing, prognosticating and improving treatment for soft tissue sarcomas. This review aims to provide an updated discussion on the known roles of specific miRNAs in the pathogenesis of sarcomas, and their potential use in prognosticating outcomes and prediction of therapeutic resistance. Full article
(This article belongs to the Topic Soft Tissue Sarcomas: Treatment and Management)
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19 pages, 1305 KiB  
Review
Mass Spectrometry-Based Proteomics Workflows in Cancer Research: The Relevance of Choosing the Right Steps
by Paula Carrillo-Rodriguez, Frode Selheim and Maria Hernandez-Valladares
Cancers 2023, 15(2), 555; https://doi.org/10.3390/cancers15020555 - 16 Jan 2023
Cited by 7 | Viewed by 5300
Abstract
The qualitative and quantitative evaluation of proteome changes that condition cancer development can be achieved with liquid chromatography–mass spectrometry (LC-MS). LC-MS-based proteomics strategies are carried out according to predesigned workflows that comprise several steps such as sample selection, sample processing including labeling, MS [...] Read more.
The qualitative and quantitative evaluation of proteome changes that condition cancer development can be achieved with liquid chromatography–mass spectrometry (LC-MS). LC-MS-based proteomics strategies are carried out according to predesigned workflows that comprise several steps such as sample selection, sample processing including labeling, MS acquisition methods, statistical treatment, and bioinformatics to understand the biological meaning of the findings and set predictive classifiers. As the choice of best options might not be straightforward, we herein review and assess past and current proteomics approaches for the discovery of new cancer biomarkers. Moreover, we review major bioinformatics tools for interpreting and visualizing proteomics results and suggest the most popular machine learning techniques for the selection of predictive biomarkers. Finally, we consider the approximation of proteomics strategies for clinical diagnosis and prognosis by discussing current barriers and proposals to circumvent them. Full article
(This article belongs to the Special Issue Application of Proteomics in Cancers)
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18 pages, 1714 KiB  
Review
Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer
by Houssein Chhouri, David Alexandre and Luca Grumolato
Cancers 2023, 15(2), 504; https://doi.org/10.3390/cancers15020504 - 13 Jan 2023
Cited by 14 | Viewed by 5183
Abstract
Non-small cell lung cancers (NSCLC) harboring activating mutations of the epidermal growth factor receptor (EGFR) are treated with specific tyrosine kinase inhibitors (EGFR-TKIs) of this receptor, resulting in clinically responses that can generally last several months. Unfortunately, EGFR-targeted therapy also favors the emergence [...] Read more.
Non-small cell lung cancers (NSCLC) harboring activating mutations of the epidermal growth factor receptor (EGFR) are treated with specific tyrosine kinase inhibitors (EGFR-TKIs) of this receptor, resulting in clinically responses that can generally last several months. Unfortunately, EGFR-targeted therapy also favors the emergence of drug tolerant or resistant cells, ultimately resulting in tumor relapse. Recently, cellular barcoding strategies have arisen as a powerful tool to investigate the clonal evolution of these subpopulations in response to anti-cancer drugs. In this review, we provide an overview of the currently available treatment options for NSCLC, focusing on EGFR targeted therapy, and discuss the common mechanisms of resistance to EGFR-TKIs. We also review the characteristics of drug-tolerant persister (DTP) cells and the mechanistic basis of drug tolerance in EGFR-mutant NSCLC. Lastly, we address how cellular barcoding can be applied to investigate the response and the behavior of DTP cells upon EGFR-TKI treatment. Full article
(This article belongs to the Special Issue Mechanisms of Acquired Resistance to Targeted Therapy)
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21 pages, 1058 KiB  
Review
Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management
by Sukanya Pati, Wadeed Irfan, Ahmad Jameel, Shahid Ahmed and Rabia K. Shahid
Cancers 2023, 15(2), 485; https://doi.org/10.3390/cancers15020485 - 12 Jan 2023
Cited by 65 | Viewed by 10067
Abstract
Background: Obesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. [...] Read more.
Background: Obesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity. Methods: A literature search using PubMed and Google Scholar was performed and the keywords ‘obesity’ and cancer’ were used. The search was limited to research papers published in English prior to September 2022 and focused on studies that investigated epidemiology, the pathogenesis of cancer, cancer incidence and the risk of recurrence, and the management of obesity. Results: About 4–8% of all cancers are attributed to obesity. Obesity is a risk factor for several major cancers, including post-menopausal breast, colorectal, endometrial, kidney, esophageal, pancreatic, liver, and gallbladder cancer. Excess body fat results in an approximately 17% increased risk of cancer-specific mortality. The relationship between obesity and the risk associated with the development of cancer and its recurrence is not fully understood and involves altered fatty acid metabolism, extracellular matrix remodeling, the secretion of adipokines and anabolic and sex hormones, immune dysregulation, and chronic inflammation. Obesity may also increase treatment-related adverse effects and influence treatment decisions regarding specific types of cancer therapy. Structured exercise in combination with dietary support and behavior therapy are effective interventions. Treatment with glucagon-like peptide-1 analogues and bariatric surgery result in more rapid weight loss and can be considered in selected cancer survivors. Conclusions: Obesity increases cancer risk and mortality. Weight-reducing strategies in obesity-associated cancers are important interventions as a key component of cancer care. Future studies are warranted to further elucidate the complex relationship between obesity and cancer with the identification of targets for effective interventions. Full article
(This article belongs to the Special Issue Environmental Carcinogenesis)
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13 pages, 521 KiB  
Review
Metastatic Prostate Cancer—A Review of Current Treatment Options and Promising New Approaches
by Philip Posdzich, Christopher Darr, Thomas Hilser, Milan Wahl, Ken Herrmann, Boris Hadaschik and Viktor Grünwald
Cancers 2023, 15(2), 461; https://doi.org/10.3390/cancers15020461 - 11 Jan 2023
Cited by 22 | Viewed by 5475
Abstract
Androgen deprivation therapy (ADT) alone has been the standard of care for many years in men with metastatic prostate cancer. Due to the limited survival under this monotherapy, many new treatment options have been developed in the last few years. Regarding hormone-sensitive prostate [...] Read more.
Androgen deprivation therapy (ADT) alone has been the standard of care for many years in men with metastatic prostate cancer. Due to the limited survival under this monotherapy, many new treatment options have been developed in the last few years. Regarding hormone-sensitive prostate cancer, combination therapies of two or three agents of ADT, androgen receptor signaling inhibitors (ARSI) and chemotherapy have been established and led to a significant benefit in overall survival. Additionally, in patients with metastatic castration-resistant prostate cancer, there are many new therapeutic approaches. Chemotherapy alone has been the standard of care in this situation. In the last years, some new therapeutic options have been developed, which led to an improved survival after progression under chemotherapy. These therapies include ARSI, PARP inhibitors and Lu-PSMA radioligand therapy. The use of a bispecific T-cell engager (BiTE) in this setting is a new promising therapeutic approach, which has not been established as standard of care yet. The role of immunotherapy in prostate cancer is still under investigation. Overall, many new treatment options make prostate cancer therapy a challenging and promising field. Full article
(This article belongs to the Special Issue Novel Therapeutics for Genitourinary Tumors)
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44 pages, 1344 KiB  
Review
DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities
by María Ovejero-Sánchez, Rogelio González-Sarmiento and Ana Belén Herrero
Cancers 2023, 15(2), 448; https://doi.org/10.3390/cancers15020448 - 10 Jan 2023
Cited by 7 | Viewed by 3333
Abstract
The DNA damage response (DDR), a set of signaling pathways for DNA damage detection and repair, maintains genomic stability when cells are exposed to endogenous or exogenous DNA-damaging agents. Alterations in these pathways are strongly associated with cancer development, including ovarian cancer (OC), [...] Read more.
The DNA damage response (DDR), a set of signaling pathways for DNA damage detection and repair, maintains genomic stability when cells are exposed to endogenous or exogenous DNA-damaging agents. Alterations in these pathways are strongly associated with cancer development, including ovarian cancer (OC), the most lethal gynecologic malignancy. In OC, failures in the DDR have been related not only to the onset but also to progression and chemoresistance. It is known that approximately half of the most frequent subtype, high-grade serous carcinoma (HGSC), exhibit defects in DNA double-strand break (DSB) repair by homologous recombination (HR), and current evidence indicates that probably all HGSCs harbor a defect in at least one DDR pathway. These defects are not restricted to HGSCs; mutations in ARID1A, which are present in 30% of endometrioid OCs and 50% of clear cell (CC) carcinomas, have also been found to confer deficiencies in DNA repair. Moreover, DDR alterations have been described in a variable percentage of the different OC subtypes. Here, we overview the main DNA repair pathways involved in the maintenance of genome stability and their deregulation in OC. We also recapitulate the preclinical and clinical data supporting the potential of targeting the DDR to fight the disease. Full article
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25 pages, 1780 KiB  
Review
The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited
by Kevin Dzobo, Dimakatso A. Senthebane and Collet Dandara
Cancers 2023, 15(2), 376; https://doi.org/10.3390/cancers15020376 - 06 Jan 2023
Cited by 43 | Viewed by 6610
Abstract
Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis, [...] Read more.
Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis, and highlight various ways through which tumor cells reprogram normal cells into phenotypes that are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to the transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells, including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic, but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to the formation of new vascular networks in order to actively promote and sustain tumor growth via the supply of oxygen and nutrients, whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to the targeting of tumor cells. The reprogramming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centered therapies under investigation. Full article
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25 pages, 7771 KiB  
Review
Risk Assessment and Pancreatic Cancer: Diagnostic Management and Artificial Intelligence
by Vincenza Granata, Roberta Fusco, Sergio Venanzio Setola, Roberta Galdiero, Nicola Maggialetti, Lucrezia Silvestro, Mario De Bellis, Elena Di Girolamo, Giulia Grazzini, Giuditta Chiti, Maria Chiara Brunese, Andrea Belli, Renato Patrone, Raffaele Palaia, Antonio Avallone, Antonella Petrillo and Francesco Izzo
Cancers 2023, 15(2), 351; https://doi.org/10.3390/cancers15020351 - 05 Jan 2023
Cited by 5 | Viewed by 2940
Abstract
Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the [...] Read more.
Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the majority of patients are diagnosed. Since surgical resection has been recognised as the only curative treatment, a PC diagnosis at the initial stage is believed the main tool to improve survival. Therefore, patient stratification according to familial and genetic risk and the creation of screening protocol by using minimally invasive diagnostic tools would be appropriate. Pancreatic cystic neoplasms (PCNs) are subsets of lesions which deserve special management to avoid overtreatment. The current PC screening programs are based on the annual employment of magnetic resonance imaging with cholangiopancreatography sequences (MR/MRCP) and/or endoscopic ultrasonography (EUS). For patients unfit for MRI, computed tomography (CT) could be proposed, although CT results in lower detection rates, compared to MRI, for small lesions. The actual major limit is the incapacity to detect and characterize the pancreatic intraepithelial neoplasia (PanIN) by EUS and MR/MRCP. The possibility of utilizing artificial intelligence models to evaluate higher-risk patients could favour the diagnosis of these entities, although more data are needed to support the real utility of these applications in the field of screening. For these motives, it would be appropriate to realize screening programs in research settings. Full article
(This article belongs to the Special Issue Diagnostics and Therapeutics Advances in Pancreatic Cancer)
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25 pages, 3043 KiB  
Review
Physical Exercise and the Hallmarks of Breast Cancer: A Narrative Review
by Celia García-Chico, Susana López-Ortiz, Saúl Peñín-Grandes, José Pinto-Fraga, Pedro L. Valenzuela, Enzo Emanuele, Claudia Ceci, Grazia Graziani, Carmen Fiuza-Luces, Simone Lista, Alejandro Lucia and Alejandro Santos-Lozano
Cancers 2023, 15(1), 324; https://doi.org/10.3390/cancers15010324 - 03 Jan 2023
Cited by 9 | Viewed by 6572
Abstract
Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, [...] Read more.
Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, (vi) resisting cell death, (vii) reprogramming energy metabolism, (viii) evading immune destruction, (ix) genome instability and mutations, (x) tumor-promoting inflammation, (xi) unlocking phenotypic plasticity, (xii) nonmutational epigenetic reprogramming, (xiii) polymorphic microbiomes, and (xiv) senescent cells. These hallmarks are also associated with the development of breast cancer, which represents the most prevalent tumor type in the world. The present narrative review aims to describe, for the first time, the effects of physical activity/exercise on these hallmarks. In summary, an active lifestyle, and particularly regular physical exercise, provides beneficial effects on all major hallmarks associated with breast cancer, and might therefore help to counteract the progression of the disease or its associated burden. Full article
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28 pages, 1054 KiB  
Review
Immunotherapy for Triple-Negative Breast Cancer: Combination Strategies to Improve Outcome
by Liying Li, Fan Zhang, Zhenyu Liu and Zhimin Fan
Cancers 2023, 15(1), 321; https://doi.org/10.3390/cancers15010321 - 03 Jan 2023
Cited by 19 | Viewed by 5442
Abstract
Due to the absence of hormone receptor (both estrogen receptors and progesterone receptors) along with human epidermal growth factor receptor 2 (HER-2) amplification, the treatment of triple-negative breast cancer (TNBC) cannot benefit from endocrine or anti-HER-2 therapy. For a long time, [...] Read more.
Due to the absence of hormone receptor (both estrogen receptors and progesterone receptors) along with human epidermal growth factor receptor 2 (HER-2) amplification, the treatment of triple-negative breast cancer (TNBC) cannot benefit from endocrine or anti-HER-2 therapy. For a long time, chemotherapy was the only systemic treatment for TNBC. Due to the lack of effective treatment options, the prognosis for TNBC is extremely poor. The successful application of immune checkpoint inhibitors (ICIs) launched the era of immunotherapy in TNBC. However, the current findings show modest efficacy of programmed cell death- (ligand) 1 (PD-(L)1) inhibitors monotherapy and only a small proportion of patients can benefit from this approach. Based on the basic principles of immunotherapy and the characteristics of the tumor immune microenvironment (TIME) in TNBC, immune combination therapy is expected to further enhance the efficacy and expand the beneficiary population of patients. Given the diversity of drugs that can be combined, it is important to select effective biomarkers to identify the target population. Moreover, the side effects associated with the combination of multiple drugs should also be considered. Full article
(This article belongs to the Special Issue Immunotherapy of Triple-Negative Breast Cancer)
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18 pages, 13914 KiB  
Review
Emerging Indications for Interventional Oncology: Expert Discussion on New Locoregional Treatments
by Roberto Iezzi, Afshin Gangi, Alessandro Posa, Uei Pua, Ping Liang, Ernesto Santos, Anil N. Kurup, Alessandro Tanzilli, Lorenzo Tenore, Davide De Leoni, Dimitrios Filippiadis, Felice Giuliante, Vincenzo Valentini, Antonio Gasbarrini, Shraga N. Goldberg, Martijn Meijerink, Riccardo Manfredi, Alexis Kelekis, Cesare Colosimo and David C. Madoff
Cancers 2023, 15(1), 308; https://doi.org/10.3390/cancers15010308 - 02 Jan 2023
Cited by 2 | Viewed by 3749
Abstract
Interventional oncology (IO) employs image-guided techniques to perform minimally invasive procedures, providing lower-risk alternatives to many traditional medical and surgical therapies for cancer patients. Since its advent, due to rapidly evolving research development, its role has expanded to encompass the diagnosis and treatment [...] Read more.
Interventional oncology (IO) employs image-guided techniques to perform minimally invasive procedures, providing lower-risk alternatives to many traditional medical and surgical therapies for cancer patients. Since its advent, due to rapidly evolving research development, its role has expanded to encompass the diagnosis and treatment of diseases across multiple body systems. In detail, interventional oncology is expanding its role across a wide spectrum of disease sites, offering a potential cure, control, or palliative care for many types of cancer patients. Due to its widespread use, a comprehensive review of the new indications for locoregional procedures is mandatory. This article summarizes the expert discussion and report from the “MIOLive Meet SIO” (Society of Interventional Oncology) session during the last MIOLive 2022 (Mediterranean Interventional Oncology Live) congress held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions. The aim of this paper is to provide an updated review of the new techniques and devices available for innovative indications not only to residents and fellows but also to colleagues approaching locoregional treatments. Full article
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20 pages, 1149 KiB  
Review
Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma
by Valentina Evdokimova, Hendrik Gassmann, Laszlo Radvanyi and Stefan E. G. Burdach
Cancers 2023, 15(1), 272; https://doi.org/10.3390/cancers15010272 - 30 Dec 2022
Cited by 13 | Viewed by 3011
Abstract
We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first [...] Read more.
We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treated with the immunotherapy approach: more than 100 years ago American surgeon William B. Coley injected his patients with a mixture of heat-inactivated bacteria, achieving survival rates apparently higher than with surgery alone. In contrast to OS which exhibits recurrent somatic copy-number alterations, EwS possesses one of the lowest mutation rates among cancers, being driven by a single oncogenic fusion protein, most frequently EWS-FLI1. In spite these differences, both EwS and OS are allied with immune tolerance and low immunogenicity. We discuss here the potential mechanisms of immune escape in these tumors, including low representation of tumor-specific antigens, low expression levels of MHC-I antigen-presenting molecules, accumulation of immunosuppressive M2 macrophages and myeloid proinflammatory cells, and release of extracellular vesicles (EVs) which are capable of reprogramming host cells in the tumor microenvironment and systemic circulation. We also discuss the vulnerabilities of EwS and OS and potential novel strategies for their targeting. Full article
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14 pages, 1645 KiB  
Review
Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors
by Alessandra Dimino, Chiara Brando, Laura Algeri, Valerio Gristina, Erika Pedone, Marta Peri, Alessandro Perez, Ida De Luca, Roberta Sciacchitano, Luigi Magrin, Tancredi Didier Bazan Russo, Marco Bono, Nadia Barraco, Silvia Contino, Maria La Mantia, Antonio Galvano, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan and Lorena Incorvaia
Cancers 2023, 15(1), 216; https://doi.org/10.3390/cancers15010216 - 29 Dec 2022
Cited by 6 | Viewed by 1461
Abstract
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies [...] Read more.
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST. Full article
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21 pages, 5981 KiB  
Article
Single-Cell Transcriptomic Profiles of Lung Pre-Metastatic Niche Reveal Neutrophil and Lymphatic Endothelial Cell Roles in Breast Cancer
by Yung-Chi Huang, Chao-Yuan Chang, Yu-Yuan Wu, Kuan-Li Wu, Ying-Ming Tsai, Hsiao-Chen Lee, Eing-Mei Tsai and Ya-Ling Hsu
Cancers 2023, 15(1), 176; https://doi.org/10.3390/cancers15010176 - 28 Dec 2022
Cited by 3 | Viewed by 3469
Abstract
The establishment of a pre-metastatic niche (PMN) is critical for cancer metastasis. However, it remains unclear as to which phenotypes induce changes in the PMN. Single-cell transcriptomic profiling of all cells of the lung in cancer-bearing MMTV-PyVT mice revealed an increased infiltration of [...] Read more.
The establishment of a pre-metastatic niche (PMN) is critical for cancer metastasis. However, it remains unclear as to which phenotypes induce changes in the PMN. Single-cell transcriptomic profiling of all cells of the lung in cancer-bearing MMTV-PyVT mice revealed an increased infiltration of N2-type neutrophils and classical monocytes associated with chronic inflammation; notably, lung neutrophils isolated from mice with primary cancer exhibited similar N2-type phenotypes and expressed high levels of inflammatory and angiogenic factors. We also discovered a new cluster of Ki67-upregulated lymphatic endothelial cells (ECs) that activated several cell division-related pathways. Receptor–ligand interactions within the lung potentially mediated PMN formation; these were exemplified by the cross talk of lymphatic EC–N2-type neutrophil via S100A6. In vitro study revealed S100A6 impaired EC tight junction and increased the transendothelial migration of neutrophils. Our results highlight the molecular mechanisms that shape lung PMN and inspire preventive strategies for lung metastasis in breast cancer. Full article
(This article belongs to the Section Molecular Cancer Biology)
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19 pages, 3444 KiB  
Article
BRAF and MEK Inhibitors and Their Toxicities: A Meta-Analysis
by Mattia Garutti, Melissa Bergnach, Jerry Polesel, Lorenza Palmero, Maria Antonietta Pizzichetta and Fabio Puglisi
Cancers 2023, 15(1), 141; https://doi.org/10.3390/cancers15010141 - 26 Dec 2022
Cited by 13 | Viewed by 2808
Abstract
Purpose: This meta-analysis summarizes the incidence of treatment-related adverse events (AE) of BRAFi and MEKi. Methods: A systematic search of Medline/PubMed was conducted to identify suitable articles published in English up to 31 December 2021. The primary outcomes were profiles for all-grade and [...] Read more.
Purpose: This meta-analysis summarizes the incidence of treatment-related adverse events (AE) of BRAFi and MEKi. Methods: A systematic search of Medline/PubMed was conducted to identify suitable articles published in English up to 31 December 2021. The primary outcomes were profiles for all-grade and grade 3 or higher treatment-related AEs, and the analysis of single side effects belonging to both categories. Results: The overall incidence of treatment-related all-grade Aes was 99% for Encorafenib (95% CI: 0.97–1.00) and 97% for Trametinib (95% CI: 0.92–0.99; I2 = 66%) and Binimetinib (95% CI: 0.94–0.99; I2 = 0%). In combined therapies, the rate was 98% for both Vemurafenib + Cobimetinib (95% CI: 0.96–0.99; I2 = 77%) and Encorafenib + Binimetinib (95% CI: 0.96–1.00). Grade 3 or higher adverse events were reported in 69% of cases for Binimetinib (95% CI: 0.50–0.84; I2 = 71%), 68% for Encorafenib (95% CI: 0.61–0.74), and 72% for Vemurafenib + Cobimetinib (95% CI: 0.65–0.79; I2 = 84%). The most common grade 1–2 AEs were pyrexia (43%) and fatigue (28%) for Dabrafenib + Trametinib and diarrhea for both Vemurafenib + Cobimetinib (52%) and Encorafenib + Binimetinib (34%). The most common AEs of grade 3 or higher were pyrexia, rash, and hypertension for Dabrafenib + Trametinib (6%), rash and hypertension for Encorafenib + Binimetinib (6%), and increased AST and ALT for Vemurafenib + Cobimetinib (10%). Conclusions: Our study provides comprehensive data on treatment-related adverse events of BRAFi and MEKi combination therapies, showing related toxicity profiles to offer a helpful tool for clinicians in the choice of therapy. Full article
(This article belongs to the Special Issue Side Effects of Anticancer Therapy: Prevention and Management)
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27 pages, 1386 KiB  
Review
CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer
by Marta Włodarczyk and Beata Pyrzynska
Cancers 2023, 15(1), 117; https://doi.org/10.3390/cancers15010117 - 24 Dec 2022
Cited by 7 | Viewed by 5653
Abstract
Chimeric antigen receptor (CAR)-modified T cell therapy has been rapidly developing in recent years, ultimately revolutionizing immunotherapeutic strategies and providing significant anti-tumor potency, mainly in treating hematological neoplasms. However, graft-versus-host disease (GVHD) and other adverse effects, such as cytokine release syndromes (CRS) and [...] Read more.
Chimeric antigen receptor (CAR)-modified T cell therapy has been rapidly developing in recent years, ultimately revolutionizing immunotherapeutic strategies and providing significant anti-tumor potency, mainly in treating hematological neoplasms. However, graft-versus-host disease (GVHD) and other adverse effects, such as cytokine release syndromes (CRS) and neurotoxicity associated with CAR-T cell infusion, have raised some concerns about the broad application of this therapy. Natural killer (NK) cells have been identified as promising alternative platforms for CAR-based therapies because of their unique features, such as a lack of human leukocyte antigen (HLA)-matching restriction, superior safety, and better anti-tumor activity when compared with CAR-T cells. The lack of CRS, neurotoxicity, or GVHD, in the case of CAR-NK therapy, in addition to the possibility of using allogeneic NK cells as a CAR platform for “off-the-shelf” therapy, opens new windows for strategic opportunities. This review underlines recent design achievements in CAR constructs and summarizes preclinical studies’ results regarding CAR-NK therapies’ safety and anti-tumor potency. Additionally, new approaches in CAR-NK technology are briefly described, and currently registered clinical trials are listed. Full article
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32 pages, 3691 KiB  
Article
Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand
by M. Isabel Acuña, Ana R. Rubio, Marta Martínez-Alonso, Natalia Busto, Ana María Rodríguez, Nerea Davila-Ferreira, Carl Smythe, Gustavo Espino, Begoña García and Fernando Domínguez
Cancers 2023, 15(1), 107; https://doi.org/10.3390/cancers15010107 - 24 Dec 2022
Cited by 3 | Viewed by 3390
Abstract
Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular [...] Read more.
Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III) complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes, especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new compounds to exploit this vulnerability. Full article
(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)
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19 pages, 801 KiB  
Review
Role of Machine Learning in Precision Oncology: Applications in Gastrointestinal Cancers
by Azadeh Tabari, Shin Mei Chan, Omar Mustafa Fathy Omar, Shams I. Iqbal, Michael S. Gee and Dania Daye
Cancers 2023, 15(1), 63; https://doi.org/10.3390/cancers15010063 - 22 Dec 2022
Cited by 10 | Viewed by 4898
Abstract
Gastrointestinal (GI) cancers, consisting of a wide spectrum of pathologies, have become a prominent health issue globally. Despite medical imaging playing a crucial role in the clinical workflow of cancers, standard evaluation of different imaging modalities may provide limited information. Accurate tumor detection, [...] Read more.
Gastrointestinal (GI) cancers, consisting of a wide spectrum of pathologies, have become a prominent health issue globally. Despite medical imaging playing a crucial role in the clinical workflow of cancers, standard evaluation of different imaging modalities may provide limited information. Accurate tumor detection, characterization, and monitoring remain a challenge. Progress in quantitative imaging analysis techniques resulted in ”radiomics”, a promising methodical tool that helps to personalize diagnosis and treatment optimization. Radiomics, a sub-field of computer vision analysis, is a bourgeoning area of interest, especially in this era of precision medicine. In the field of oncology, radiomics has been described as a tool to aid in the diagnosis, classification, and categorization of malignancies and to predict outcomes using various endpoints. In addition, machine learning is a technique for analyzing and predicting by learning from sample data, finding patterns in it, and applying it to new data. Machine learning has been increasingly applied in this field, where it is being studied in image diagnosis. This review assesses the current landscape of radiomics and methodological processes in GI cancers (including gastric, colorectal, liver, pancreatic, neuroendocrine, GI stromal, and rectal cancers). We explain in a stepwise fashion the process from data acquisition and curation to segmentation and feature extraction. Furthermore, the applications of radiomics for diagnosis, staging, assessment of tumor prognosis and treatment response according to different GI cancer types are explored. Finally, we discussed the existing challenges and limitations of radiomics in abdominal cancers and investigate future opportunities. Full article
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12 pages, 1091 KiB  
Article
Low-Energy X-Ray Intraoperative Radiation Therapy (Lex-IORT) for Resected Brain Metastases: A Single-Institution Experience
by Christian D. Diehl, Steffi U. Pigorsch, Jens Gempt, Sandro M. Krieg, Silvia Reitz, Maria Waltenberger, Melanie Barz, Hanno S. Meyer, Arthur Wagner, Jan Wilkens, Benedikt Wiestler, Claus Zimmer, Bernhard Meyer and Stephanie E. Combs
Cancers 2023, 15(1), 14; https://doi.org/10.3390/cancers15010014 - 20 Dec 2022
Cited by 8 | Viewed by 1506
Abstract
Background: Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest. Method: Eighteen consecutive [...] Read more.
Background: Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest. Method: Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16–30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-specific, radiographic and clinical data were reviewed to evaluate the effectiveness and safety of IORT for BM. Descriptive statistics and Kaplan–Meyer analysis were applied. Results: The mean follow-up time was 10.8 months (range, 0–39 months). The estimated local control (LC), distant brain control (DBC) and overall survival (OS) at 12 months post IORT were 92.9% (95%-CI 79.3–100%), 71.4% (95%-CI 50.2–92.6%) and 58.0% (95%-CI 34.1–81.9%), respectively. Two patients developed radiation necrosis (11.1%) and wound infection (CTCAE grade III); both had additional adjuvant treatment after IORT. For five patients (27.8%), the time to the start or continuation of systemic treatment was ≤15 days and hence shorter than wound healing and adjuvant RT would have required. Conclusion: In accordance with previous series, this study demonstrates the effectiveness and safety of IORT in the management of brain metastases despite the small cohort and the retrospective characteristic of this analysis. Full article
(This article belongs to the Special Issue Advances in Modern Radiation Oncology)
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18 pages, 2854 KiB  
Review
Liver Microenvironment Response to Prostate Cancer Metastasis and Hormonal Therapy
by Alison K. Buxton, Salma Abbasova, Charlotte L. Bevan and Damien A. Leach
Cancers 2022, 14(24), 6189; https://doi.org/10.3390/cancers14246189 - 15 Dec 2022
Cited by 4 | Viewed by 3017
Abstract
Prostate cancer-associated deaths arise from disease progression and metastasis. Metastasis to the liver is associated with the worst clinical outcomes for prostate cancer patients, and these metastatic tumors can be particularly resistant to the currently widely used chemotherapy and hormonal therapies, such as [...] Read more.
Prostate cancer-associated deaths arise from disease progression and metastasis. Metastasis to the liver is associated with the worst clinical outcomes for prostate cancer patients, and these metastatic tumors can be particularly resistant to the currently widely used chemotherapy and hormonal therapies, such as anti-androgens which block androgen synthesis or directly target the androgen receptor. The incidence of liver metastases is reportedly increasing, with a potential correlation with use of anti-androgen therapies. A key player in prostate cancer progression and therapeutic response is the microenvironment of the tumor(s). This is a dynamic and adaptive collection of cells and proteins, which impart signals and stimuli that can alter biological processes within prostate cancer cells. Investigation in the prostate primary site has demonstrated that cells of the microenvironment are also responsive to hormones and hormonal therapies. In this review, we collate information about what happens when cancer moves to the liver: the types of prostate cancer cells that metastasize there, the response of resident mesenchymal cells of the liver, and how the interactions between the cancer cells and the microenvironment may be altered by hormonal therapy. Full article
(This article belongs to the Special Issue Prostate Cancer: Pathophysiology, Pathology and Therapy)
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17 pages, 2313 KiB  
Article
TP53 Co-Mutation Status Association with Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer
by Xiuning Le, Cliff Molife, Mark S. Leusch, Maria Teresa Rizzo, Patrick M. Peterson, Nicola Caria, Yongmei Chen, Elena Gonzalez Gugel and Carla Visseren-Grul
Cancers 2022, 14(24), 6127; https://doi.org/10.3390/cancers14246127 - 12 Dec 2022
Cited by 8 | Viewed by 1702
Abstract
TP53 co-mutations have shown association with poor prognosis in various solid tumors. For EGFR-mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic [...] Read more.
TP53 co-mutations have shown association with poor prognosis in various solid tumors. For EGFR-mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic database. Patients who initiated therapy for EGFR-mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by TP53-mutational status. In 356 eligible EGFR-mutated aNSCLC patients (median age 68 years), 210 (59.0%) had TP53 co-mutation and 146 (41.0%) had TP53 wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with TP53 co-mutation versus TP53 wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1–1.9, p = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1–2.2, p = 0.0088). Multivariable analysis confirmed independent association between TP53 co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0–0.9, p = 0.0280) and OS (HR = 1.4, 95% CI 1.0–2.0, p = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by EGFR-activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L EGFR-TKI subgroup. TP53 co-mutations negatively affected survival in patients with EGFR-mutated aNSCLC receiving standard 1 L therapy in real-world practice. Full article
(This article belongs to the Special Issue Actionable Mutations in Lung Cancer)
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16 pages, 1610 KiB  
Article
Dual NGS Comparative Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Samples of Non-Small Cell Lung Carcinoma (NSCLC)
by Laura Buburuzan, Maria-Anca Zamfir (Irofei), Carmen Maria Ardeleanu, Alin Horatiu Muresan, Florina Vasilescu, Ariana Hudita, Marieta Costache, Bianca Galateanu, Alexandra Puscasu, Alexandru Filippi and Natalia Motas
Cancers 2022, 14(24), 6084; https://doi.org/10.3390/cancers14246084 - 10 Dec 2022
Viewed by 2871
Abstract
Lung cancer ranks second worldwide after breast cancer and third in Europe after breast and colorectal cancers when both sexes and all ages are considered. In this context, the aim of this study was to emphasize the power of dual analysis of the [...] Read more.
Lung cancer ranks second worldwide after breast cancer and third in Europe after breast and colorectal cancers when both sexes and all ages are considered. In this context, the aim of this study was to emphasize the power of dual analysis of the molecular profile both in tumor tissue and plasma by NGS assay as a liquid biopsy approach with impact on prognosis and therapy modulation in NSCLC patients. NGS analysis was performed both from tissue biopsies and from cfNAs isolated from peripheral blood samples. Out of all 29 different mutations detectable by both NGS panels (plasma and tumor tissue), seven different variants (24.13%; EGFR L858R in two patients, KRAS G13D and Q61H and TP53 G244D, V197M, R213P, and R273H) were detected only in plasma and not in the tumor itself. These mutations were detected in seven different patients, two of them having known distant organ metastasis. Our data show that NGS analysis of cfDNA could identify actionable mutations in advanced NSCLC and, therefore, this analysis could be used to monitor the disease progression and the treatment response and even to modulate the therapy in real time. Full article
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56 pages, 2099 KiB  
Review
Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?
by Mariana Tannoury, Delphine Garnier, Santos A. Susin and Brigitte Bauvois
Cancers 2022, 14(24), 6026; https://doi.org/10.3390/cancers14246026 - 07 Dec 2022
Cited by 4 | Viewed by 3105
Abstract
Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of [...] Read more.
Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton’s tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders. Full article
(This article belongs to the Section Cancer Biomarkers)
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39 pages, 8167 KiB  
Article
Integrating Pharmacogenomics Data-Driven Computational Drug Prediction with Single-Cell RNAseq to Demonstrate the Efficacy of a NAMPT Inhibitor against Aggressive, Taxane-Resistant, and Stem-like Cells in Lethal Prostate Cancer
by Suman Mazumder, Taraswi Mitra Ghosh, Ujjal K. Mukherjee, Sayak Chakravarti, Farshad Amiri, Razan S. Waliagha, Farnaz Hemmati, Panagiotis Mistriotis, Salsabil Ahmed, Isra Elhussin, Ahmad-Bin Salam, Windy Dean-Colomb, Clayton Yates, Robert D. Arnold and Amit K. Mitra
Cancers 2022, 14(23), 6009; https://doi.org/10.3390/cancers14236009 - 06 Dec 2022
Cited by 2 | Viewed by 3227
Abstract
Metastatic prostate cancer/PCa is the second leading cause of cancer deaths in US men. Most early-stage PCa are dependent on overexpression of the androgen receptor (AR) and, therefore, androgen deprivation therapies/ADT-sensitive. However, eventual resistance to standard medical castration (AR-inhibitors) and secondary chemotherapies (taxanes) [...] Read more.
Metastatic prostate cancer/PCa is the second leading cause of cancer deaths in US men. Most early-stage PCa are dependent on overexpression of the androgen receptor (AR) and, therefore, androgen deprivation therapies/ADT-sensitive. However, eventual resistance to standard medical castration (AR-inhibitors) and secondary chemotherapies (taxanes) is nearly universal. Further, the presence of cancer stem-like cells (EMT/epithelial-to-mesenchymal transdifferentiation) and neuroendocrine PCa (NEPC) subtypes significantly contribute to aggressive/lethal/advanced variants of PCa (AVPC). In this study, we introduced a pharmacogenomics data-driven optimization-regularization-based computational prediction algorithm (“secDrugs”) to predict novel drugs against lethal PCa. Integrating secDrug with single-cell RNA-sequencing/scRNAseq as a ‘Double-Hit’ drug screening tool, we demonstrated that single-cells representing drug-resistant and stem-cell-like cells showed high expression of the NAMPT pathway genes, indicating potential efficacy of the secDrug FK866 which targets NAMPT. Next, using several cell-based assays, we showed substantial impact of FK866 on clinically advanced PCa as a single agent and in combination with taxanes or AR-inhibitors. Bulk-RNAseq and scRNAseq revealed that, in addition to NAMPT inhibition, FK866 regulates tumor metastasis, cell migration, invasion, DNA repair machinery, redox homeostasis, autophagy, as well as cancer stemness–related genes, HES1 and CD44. Further, we combined a microfluidic chip-based cell migration assay with a traditional cell migration/‘scratch’ assay and demonstrated that FK866 reduces cancer cell invasion and motility, indicating abrogation of metastasis. Finally, using PCa patient datasets, we showed that FK866 is potentially capable of reversing the expression of several genes associated with biochemical recurrence, including IFITM3 and LTB4R. Thus, using FK866 as a proof-of-concept candidate for drug repurposing, we introduced a novel, universally applicable preclinical drug development pipeline to circumvent subclonal aggressiveness, drug resistance, and stemness in lethal PCa. Full article
(This article belongs to the Special Issue Prostate Cancer: Pathophysiology, Pathology and Therapy)
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30 pages, 1375 KiB  
Review
Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors
by Qiuqiang Chen, Lingeng Lu and Wenxue Ma
Cancers 2022, 14(23), 5983; https://doi.org/10.3390/cancers14235983 - 03 Dec 2022
Cited by 6 | Viewed by 2885
Abstract
Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy [...] Read more.
Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy has exhibited conspicuous clinical efficacy in hematological malignancies, but more than half of patients will relapse. Of note, the efficacy of CAR T-cell therapy has been even more disappointing in solid tumors. These challenges mainly include (1) the failures of CAR T-cells to treat highly heterogeneous solid tumors due to the difficulty in identifying unique tumor antigen targets, (2) the expression of target antigens in non-cancer cells, (3) the inability of CAR T-cells to effectively infiltrate solid tumors, (4) the short lifespan and lack of persistence of CAR T-cells, and (5) cytokine release syndrome and neurotoxicity. In combination with these characteristics, the ideal CAR T-cell therapy for solid tumors should maintain adequate T-cell response over a long term while sparing healthy tissues. This article reviewed the status, clinical application, efficacy, safety, and challenges of CAR T-cell therapies, as well as the latest progress of CAR T-cell therapies for solid tumors. In addition, the potential strategies to improve the efficacy of CAR T-cells and prevent side effects in solid tumors were also explored. Full article
(This article belongs to the Special Issue Cytokines in Clinical Cancer Immunotherapy)
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9 pages, 246 KiB  
Review
Circulating Human Papillomavirus DNA in Head and Neck Squamous Cell Carcinoma: Possible Applications and Future Directions
by Dauren Adilbay, Saudamini Lele, John Pang, Ameya Asarkar, Jason Calligas and Cherie-Ann Nathan
Cancers 2022, 14(23), 5946; https://doi.org/10.3390/cancers14235946 - 01 Dec 2022
Cited by 8 | Viewed by 1509
Abstract
There has been a rising trend in HPV-induced head and neck cancers in the last several decades. This subgroup of squamous cell carcinoma is mostly located in the oropharynx and comprises a subset of patients who are typically younger and without the usual [...] Read more.
There has been a rising trend in HPV-induced head and neck cancers in the last several decades. This subgroup of squamous cell carcinoma is mostly located in the oropharynx and comprises a subset of patients who are typically younger and without the usual risk factors of smoking and alcohol use. As the prognosis of HPV-induced OPC is more favorable, there is a desire to properly select these patients for de-intensification protocols while identifying individuals who may suffer treatment failure. Here, we describe recent developments in circulating tumor HPV DNA as a marker of HPV-positive oropharyngeal cancer that can potentially be used as a diagnostic tool to stratify patients for de-escalation strategies and to survey for recurrence. Full article
(This article belongs to the Special Issue Epidemiology of HPV-Associated Oropharyngeal Squamous Cell Carcinoma)
15 pages, 4023 KiB  
Article
Regression of Lung Cancer in Mice by Intranasal Administration of SARS-CoV-2 Spike S1
by Monica Sheinin, Brian Jeong, Ramesh K. Paidi and Kalipada Pahan
Cancers 2022, 14(22), 5648; https://doi.org/10.3390/cancers14225648 - 17 Nov 2022
Cited by 9 | Viewed by 6081
Abstract
This study underlines the importance of SARS-CoV-2 spike S1 in prompting death in cultured non-small cell lung cancer (NSCLC) cells and in vivo in lung tumors in mice. Interestingly, we found that recombinant spike S1 treatment at very low doses led to death [...] Read more.
This study underlines the importance of SARS-CoV-2 spike S1 in prompting death in cultured non-small cell lung cancer (NSCLC) cells and in vivo in lung tumors in mice. Interestingly, we found that recombinant spike S1 treatment at very low doses led to death of human A549 NSCLC cells. On the other hand, boiled recombinant SARS-CoV-2 spike S1 remained unable to induce death, suggesting that the induction of cell death in A549 cells was due to native SARS-CoV-2 spike S1 protein. SARS-CoV-2 spike S1-induced A549 cell death was also inhibited by neutralizing antibodies against spike S1 and ACE2. Moreover, our newly designed wild type ACE2-interacting domain of SARS-CoV-2 (wtAIDS), but not mAIDS, peptide also attenuated SARS-CoV-2 spike S1-induced cell death, suggesting that SARS-CoV-2 spike S1-induced death in A549 NSCLC cells depends on its interaction with ACE2 receptor. Similarly, recombinant spike S1 treatment also led to death of human H1299 and H358 NSCLC cells. Finally, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) intoxication led to the formation tumors in lungs of A/J mice and alternate day intranasal treatment with low dose of recombinant SARS-CoV-2 spike S1 from 22-weeks of NNK insult (late stage) induced apoptosis and tumor regression in the lungs. These studies indicate that SARS-CoV-2 spike S1 may have implications for lung cancer treatment. Full article
(This article belongs to the Section Cancer Therapy)
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19 pages, 4696 KiB  
Article
Gambogic Acid Induces Pyroptosis of Colorectal Cancer Cells through the GSDME-Dependent Pathway and Elicits an Antitumor Immune Response
by Hanjie Xu, Danya Zhang, Rui Wei, Ying Zhou, Geyang Dai, Jie Li, Yue Sun, Fei Li and Ling Xi
Cancers 2022, 14(22), 5505; https://doi.org/10.3390/cancers14225505 - 09 Nov 2022
Cited by 10 | Viewed by 2158
Abstract
Pyroptosis is a recently identified form of programmed cell death (PCD) that exerts a vital influence on the antitumor immune response. GA, a xanthone structure isolated from gamboge resin, is a naturally occurring bioactive ingredient with several anticancer activities, such as activities that [...] Read more.
Pyroptosis is a recently identified form of programmed cell death (PCD) that exerts a vital influence on the antitumor immune response. GA, a xanthone structure isolated from gamboge resin, is a naturally occurring bioactive ingredient with several anticancer activities, such as activities that affect cell cycle arrest, apoptosis, and autophagy. Here, we found that GA decreased the viability of the CRC cell lines, HCT116 and CT26, in a dose- and time-dependent manner, and multiple pores and large bubbles in the membranes, which are morphological characteristics of pyroptosis, were observed by light microscopy and transmission electron microscopy (TEM). Furthermore, the cleavage of gasdermin E (GSDME) was observed after exposure to GA, along with concomitant activation of caspase-3. Additionally, GSDME-dependent pyroptosis triggered by GA could be attenuated by siRNA-mediated knockdown of GSDME and treatment with the caspase-3 inhibitor. Moreover, we found that GA induced pyroptosis and significantly inhibited tumor growth in CT26 tumor-bearing mice. Strikingly, significantly increased proportions of CD3+ T cells, cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) were observed in the tumor microenvironment in the GA-treated groups. Moreover, significantly increased proportions of CTLs and effector memory T cells (TEM) (CD8+ CD44+ CD62L) were also detected in the spleens of the GA-treated groups, suggesting that the pyroptosis-induced immune response generated a robust memory response that mediated protective immunity. In this study, we revealed a previously unrecognized mechanism by which GA induces GSDME-dependent pyroptosis and enhances the anticancer immune response. Based on this mechanism, GA is a promising antitumor drug for CRC treatment that induces caspase-3-GSDME-dependent pyroptosis. This study provides novel insight into cancer chemoimmunotherapy. Full article
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10 pages, 514 KiB  
Article
Global Association of COVID-19 Pandemic Measures with Cancer Treatment: A Systematic Review and Meta-Analysis
by Federica Teglia, Marco Angelini, Giulia Casolari, Laura Astolfi and Paolo Boffetta
Cancers 2022, 14(22), 5490; https://doi.org/10.3390/cancers14225490 - 08 Nov 2022
Cited by 11 | Viewed by 1295
Abstract
Importance: The COVID-19 pandemic has put a serious strain on health services, including cancer treatment. Objective: This study aimed to investigate the changes in cancer treatment worldwide during the first phase of the SARS-CoV-2 outbreak. Data Sources: Pubmed, Proquest, and Scopus databases were [...] Read more.
Importance: The COVID-19 pandemic has put a serious strain on health services, including cancer treatment. Objective: This study aimed to investigate the changes in cancer treatment worldwide during the first phase of the SARS-CoV-2 outbreak. Data Sources: Pubmed, Proquest, and Scopus databases were searched comprehensively for articles published between 1 January 2020 and 12 December 2021, in order to perform a systematic review and meta-analysis conducted following the PRISMA statement. Study Selection: Studies and articles that reported data on the number of or variation in cancer treatments between the pandemic and pre-pandemic periods, comprising oncological surgery, radiotherapy, and systemic therapies, were included. Data Extraction and Synthesis: Data were extracted from two pairs of independent reviewers. The weighted average of the percentage variation was calculated between the two periods to assess the change in the number of cancer treatments performed during the pandemic. Stratified analyses were performed by type of treatment, geographic area, time period, study setting, and type of cancer. Results: Among the 47 articles retained, we found an overall reduction of −18.7% (95% CI, −24.1 to −13.3) in the total number of cancer treatments administered during the COVID-19 pandemic compared to the previous periods. Surgical treatment had a larger decrease compared to medical treatment (−33.9% versus −12.6%). For all three types of treatments, we identified a U-shaped temporal trend during the entire period January–October 2020. Significant decreases were also identified for different types of cancer, in particular for skin cancer (−34.7% [95% CI, −46.8 to −22.5]) and for all geographic areas, in particular, Asia (−42.1% [95% CI, −49.6 to −34.7]). Conclusions and Relevance: The interruption, delay, and modifications to cancer treatment due to the COVID-19 pandemic are expected to alter the quality of care and patient outcomes. Full article
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18 pages, 1880 KiB  
Article
An Effective Method for Lung Cancer Diagnosis from CT Scan Using Deep Learning-Based Support Vector Network
by Imran Shafi, Sadia Din, Asim Khan, Isabel De La Torre Díez, Ramón del Jesús Palí Casanova, Kilian Tutusaus Pifarre and Imran Ashraf
Cancers 2022, 14(21), 5457; https://doi.org/10.3390/cancers14215457 - 06 Nov 2022
Cited by 20 | Viewed by 6785
Abstract
The diagnosis of early-stage lung cancer is challenging due to its asymptomatic nature, especially given the repeated radiation exposure and high cost of computed tomography(CT). Examining the lung CT images to detect pulmonary nodules, especially the cell lung cancer lesions, is also tedious [...] Read more.
The diagnosis of early-stage lung cancer is challenging due to its asymptomatic nature, especially given the repeated radiation exposure and high cost of computed tomography(CT). Examining the lung CT images to detect pulmonary nodules, especially the cell lung cancer lesions, is also tedious and prone to errors even by a specialist. This study proposes a cancer diagnostic model based on a deep learning-enabled support vector machine (SVM). The proposed computer-aided design (CAD) model identifies the physiological and pathological changes in the soft tissues of the cross-section in lung cancer lesions. The model is first trained to recognize lung cancer by measuring and comparing the selected profile values in CT images obtained from patients and control patients at their diagnosis. Then, the model is tested and validated using the CT scans of both patients and control patients that are not shown in the training phase. The study investigates 888 annotated CT scans from the publicly available LIDC/IDRI database. The proposed deep learning-assisted SVM-based model yields 94% accuracy for pulmonary nodule detection representing early-stage lung cancer. It is found superior to other existing methods including complex deep learning, simple machine learning, and the hybrid techniques used on lung CT images for nodule detection. Experimental results demonstrate that the proposed approach can greatly assist radiologists in detecting early lung cancer and facilitating the timely management of patients. Full article
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43 pages, 2814 KiB  
Review
Physical Activity as the Best Supportive Care in Cancer: The Clinician’s and the Researcher’s Perspectives
by Cécile Torregrosa, Frédéric Chorin, Eva Ester Molina Beltran, Cindy Neuzillet and Victoire Cardot-Ruffino
Cancers 2022, 14(21), 5402; https://doi.org/10.3390/cancers14215402 - 02 Nov 2022
Cited by 10 | Viewed by 6722
Abstract
Multidisciplinary supportive care, integrating the dimensions of exercise alongside oncological treatments, is now regarded as a new paradigm to improve patient survival and quality of life. Its impact is important on the factors that control tumor development, such as the immune system, inflammation, [...] Read more.
Multidisciplinary supportive care, integrating the dimensions of exercise alongside oncological treatments, is now regarded as a new paradigm to improve patient survival and quality of life. Its impact is important on the factors that control tumor development, such as the immune system, inflammation, tissue perfusion, hypoxia, insulin resistance, metabolism, glucocorticoid levels, and cachexia. An increasing amount of research has been published in the last years on the effects of physical activity within the framework of oncology, marking the appearance of a new medical field, commonly known as “exercise oncology”. This emerging research field is trying to determine the biological mechanisms by which, aerobic exercise affects the incidence of cancer, the progression and/or the appearance of metastases. We propose an overview of the current state of the art physical exercise interventions in the management of cancer patients, including a pragmatic perspective with tips for routine practice. We then develop the emerging mechanistic views about physical exercise and their potential clinical applications. Moving toward a more personalized, integrated, patient-centered, and multidisciplinary management, by trying to understand the different interactions between the cancer and the host, as well as the impact of the disease and the treatments on the different organs, this seems to be the most promising method to improve the care of cancer patients. Full article
(This article belongs to the Special Issue Physical Activity and Cancer Care)
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12 pages, 2080 KiB  
Article
Predicting Malignant Lymph Nodes Using a Novel Scoring System Based on Multi-Endobronchial Ultrasound Features
by Momoko Morishita, Keigo Uchimura, Hideaki Furuse, Tatsuya Imabayashi, Takaaki Tsuchida and Yuji Matsumoto
Cancers 2022, 14(21), 5355; https://doi.org/10.3390/cancers14215355 - 30 Oct 2022
Cited by 2 | Viewed by 8521
Abstract
Endobronchial ultrasound (EBUS) features with B-, power/color Doppler, and elastography modes help differentiate between benign and malignant lymph nodes (MLNs) during transbronchial needle aspiration (TBNA); however, only few studies have assessed them simultaneously. We evaluated the diagnostic accuracy of each EBUS feature and [...] Read more.
Endobronchial ultrasound (EBUS) features with B-, power/color Doppler, and elastography modes help differentiate between benign and malignant lymph nodes (MLNs) during transbronchial needle aspiration (TBNA); however, only few studies have assessed them simultaneously. We evaluated the diagnostic accuracy of each EBUS feature and aimed to establish a scoring system to predict MLNs. EBUS features of consecutive patients and final diagnosis per lymph node (LN) were examined retrospectively. In total, 594 LNs from 301 patients were analyzed. Univariable analyses revealed that EBUS features, except for round shape, could differentiate MLNs from benign LNs. Multivariable analysis revealed that short axis (>1 cm), heterogeneous echogenicity, absence of central hilar structure, presence of coagulation necrosis sign, and blue-dominant elastographic images were independent predictors of MLNs. At three or more EBUS features predicting MLNs, our scoring system had high sensitivity (77.9%) and specificity (91.8%). The area under the receiver operating curve (AUC) was 0.894 (95% confidence interval (CI): 0.868–0.920), which was higher than that of B-mode features alone (AUC: 0.840 (95% CI: 0.807–0.873)). The novel scoring system could predict MLNs more accurately than B-mode features alone. Multi-EBUS features may increase EBUS-TBNA efficiency for LN evaluation. Full article
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27 pages, 3015 KiB  
Review
In Vivo Models for Prostate Cancer Research
by Robert Adamiecki, Anita Hryniewicz-Jankowska, Maria A. Ortiz, Xiang Li, Baylee A. Porter-Hansen, Imad Nsouli, Gennady Bratslavsky and Leszek Kotula
Cancers 2022, 14(21), 5321; https://doi.org/10.3390/cancers14215321 - 28 Oct 2022
Cited by 4 | Viewed by 2753
Abstract
In 2022, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer in men in the United States—almost 270,000 American men are estimated to be diagnosed with PCa in 2022. This review compares and contrasts in vivo models of PCa with [...] Read more.
In 2022, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer in men in the United States—almost 270,000 American men are estimated to be diagnosed with PCa in 2022. This review compares and contrasts in vivo models of PCa with regards to the altered genes, signaling pathways, and stages of tumor progression associated with each model. The main type of model included in this review are genetically engineered mouse models, which include conditional and constitutive knockout model. 2D cell lines, 3D organoids and spheroids, xenografts and allografts, and patient derived models are also included. The major applications, advantages and disadvantages, and ease of use and cost are unique to each type of model, but they all make it easier to translate the tumor progression that is seen in the mouse prostate to the human prostate. Although both human and mouse prostates are androgen-dependent, the fact that the native, genetically unaltered prostate in mice cannot give rise to carcinoma is an especially critical component of PCa models. Thanks to the similarities between the mouse and human genome, our knowledge of PCa has been expanded, and will continue to do so, through models of PCa. Full article
(This article belongs to the Topic Animal Model in Biomedical Research, 2nd Volume)
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30 pages, 36396 KiB  
Article
A Soft Label Deep Learning to Assist Breast Cancer Target Therapy and Thyroid Cancer Diagnosis
by Ching-Wei Wang, Kuan-Yu Lin, Yi-Jia Lin, Muhammad-Adil Khalil, Kai-Lin Chu and Tai-Kuang Chao
Cancers 2022, 14(21), 5312; https://doi.org/10.3390/cancers14215312 - 28 Oct 2022
Cited by 8 | Viewed by 1966
Abstract
According to the World Health Organization Report 2022, cancer is the most common cause of death contributing to nearly one out of six deaths worldwide. Early cancer diagnosis and prognosis have become essential in reducing the mortality rate. On the other hand, cancer [...] Read more.
According to the World Health Organization Report 2022, cancer is the most common cause of death contributing to nearly one out of six deaths worldwide. Early cancer diagnosis and prognosis have become essential in reducing the mortality rate. On the other hand, cancer detection is a challenging task in cancer pathology. Trained pathologists can detect cancer, but their decisions are subjective to high intra- and inter-observer variability, which can lead to poor patient care owing to false-positive and false-negative results. In this study, we present a soft label fully convolutional network (SL-FCN) to assist in breast cancer target therapy and thyroid cancer diagnosis, using four datasets. To aid in breast cancer target therapy, the proposed method automatically segments human epidermal growth factor receptor 2 (HER2) amplification in fluorescence in situ hybridization (FISH) and dual in situ hybridization (DISH) images. To help in thyroid cancer diagnosis, the proposed method automatically segments papillary thyroid carcinoma (PTC) on Papanicolaou-stained fine needle aspiration and thin prep whole slide images (WSIs). In the evaluation of segmentation of HER2 amplification in FISH and DISH images, we compare the proposed method with thirteen deep learning approaches, including U-Net, U-Net with InceptionV5, Ensemble of U-Net with Inception-v4, Inception-Resnet-v2 encoder, and ResNet-34 encoder, SegNet, FCN, modified FCN, YOLOv5, CPN, SOLOv2, BCNet, and DeepLabv3+ with three different backbones, including MobileNet, ResNet, and Xception, on three clinical datasets, including two DISH datasets on two different magnification levels and a FISH dataset. The result on DISH breast dataset 1 shows that the proposed method achieves high accuracy of 87.77 ± 14.97%, recall of 91.20 ± 7.72%, and F1-score of 81.67 ± 17.76%, while, on DISH breast dataset 2, the proposed method achieves high accuracy of 94.64 ± 2.23%, recall of 83.78 ± 6.42%, and F1-score of 85.14 ± 6.61% and, on the FISH breast dataset, the proposed method achieves high accuracy of 93.54 ± 5.24%, recall of 83.52 ± 13.15%, and F1-score of 86.98 ± 9.85%, respectively. Furthermore, the proposed method outperforms most of the benchmark approaches by a significant margin (p <0.001). In evaluation of segmentation of PTC on Papanicolaou-stained WSIs, the proposed method is compared with three deep learning methods, including Modified FCN, U-Net, and SegNet. The experimental result demonstrates that the proposed method achieves high accuracy of 99.99 ± 0.01%, precision of 92.02 ± 16.6%, recall of 90.90 ± 14.25%, and F1-score of 89.82 ± 14.92% and significantly outperforms the baseline methods, including U-Net and FCN (p <0.001). With the high degree of accuracy, precision, and recall, the results show that the proposed method could be used in assisting breast cancer target therapy and thyroid cancer diagnosis with faster evaluation and minimizing human judgment errors. Full article
(This article belongs to the Special Issue Clinical Perspective and Translational Oncology of Liquid Biopsy)
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