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14 pages, 276 KiB

Open AccessReview

Emerging Advances in Endometrial Cancer: Integration of Molecular Classification into Staging for Enhanced Prognostic Accuracy and Implications for Racial Disparities

by Joy Ogunmuyiwa and Vonetta Williams

Cancers 2024, 16(6), 1172; https://doi.org/10.3390/cancers16061172 - 16 Mar 2024

Viewed by 834

Abstract

Since the 2009 FIGO staging update, focused exclusively on the anatomic extent of disease, there have been several advances in the understanding of the pathologic and molecular features of endometrial cancer. In a significant departure from the 2009 FIGO staging system, the 2023 [...] Read more.

Since the 2009 FIGO staging update, focused exclusively on the anatomic extent of disease, there have been several advances in the understanding of the pathologic and molecular features of endometrial cancer. In a significant departure from the 2009 FIGO staging system, the 2023 FIGO staging update integrates both histopathological and molecular classification. With the inclusion of non-anatomic pathologic parameters such as histology, tumor grade, lymphovascular space invasion, and molecular subtype, the 2023 FIGO staging update aims to create more clinically relevant substages that improve prognostic value and allows for more individualized treatment paradigms. This review will evaluate the clinical impact of the 2023 FIGO staging update, describe the stage shifts that lead to higher prognostic precision, and illustrate the current state of molecular analysis in clinical practice. Furthermore, this review will explore how incorporating factors such as molecular subtype into endometrial cancer staging can offer valuable insights into the racial disparities seen in morbidity and mortality. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

14 pages, 1525 KiB

Open AccessReview

Electroporation in Translational Medicine: From Veterinary Experience to Human Oncology

by Enrico P. Spugnini, Maria Condello, Stefania Crispi and Alfonso Baldi

Cancers 2024, 16(5), 1067; https://doi.org/10.3390/cancers16051067 - 06 Mar 2024

Viewed by 697

Abstract

Electroporation (EP) is a broadly accepted procedure that, through the application of electric pulses with appropriate amplitudes and waveforms, promotes the delivery of anticancer molecules in various oncology therapies. EP considerably boosts the absorptivity of targeted cells to anticancer molecules of different natures, [...] Read more.

Electroporation (EP) is a broadly accepted procedure that, through the application of electric pulses with appropriate amplitudes and waveforms, promotes the delivery of anticancer molecules in various oncology therapies. EP considerably boosts the absorptivity of targeted cells to anticancer molecules of different natures, thus upgrading their effectiveness. Its use in veterinary oncology has been widely explored, and some applications, such as electrochemotherapy (ECT), are currently approved as first-line treatments for several neoplastic conditions. Other applications include irreversible electroporation and EP-based cancer vaccines. In human oncology, EP is still mostly restricted to therapies for cutaneous tumors and the palliation of cutaneous and visceral metastases of malignant tumors. Fields where veterinary experience could help smooth the clinical transition to humans include intraoperative EP, interventional medicine and cancer vaccines. This article recapitulates the state of the art of EP in veterinary and human oncology, recounting the most relevant results to date. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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14 pages, 776 KiB

Open AccessReview

Immune Effector Cell-Associated HLH-like Syndrome: A Review of the Literature of an Increasingly Recognized Entity

by Tyler Fugere, Alan Baltz, Akash Mukherjee, Mamatha Gaddam, Ankur Varma, Muthu Veeraputhiran and Cesar Giancarlo Gentille Sanchez

Cancers 2023, 15(21), 5149; https://doi.org/10.3390/cancers15215149 - 26 Oct 2023

Cited by 2 | Viewed by 1499

Abstract

Since CAR-T cell therapy was initially approved in 2017, its use has become more prevalent and so have its side effects. CAR-T-related HLH, also named immune effector cell-associated HLH-like syndrome (IEC-HS), is a rare but fatal toxicity if not recognized promptly. We conducted [...] Read more.

Since CAR-T cell therapy was initially approved in 2017, its use has become more prevalent and so have its side effects. CAR-T-related HLH, also named immune effector cell-associated HLH-like syndrome (IEC-HS), is a rare but fatal toxicity if not recognized promptly. We conducted a review of the literature in order to understand the prevalence of IEC-HS as well as clarify the evolution of the diagnostic criteria and treatment recommendations. IEC-HS occurrence varies between CAR-T cell products and the type of malignancy treated. Diagnosis can be challenging as there are no standardized diagnostic criteria, and its clinical features can overlap with cytokine release syndrome and active hematological disease. Suggested treatment strategies have been extrapolated from prior experience in HLH and include anakinra, corticosteroids and ruxolitinib. IEC-HS is a potentially fatal toxicity associated with CAR-T cell therapy. Early recognition with reliable diagnostic criteria and prompt implementation of treatment specific to IEC-HS is imperative for improving patient outcomes. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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18 pages, 1439 KiB

Open AccessReview

Biomarkers in Laryngeal Squamous Cell Carcinoma: The Literature Review

by Barbara Verro, Carmelo Saraniti, Daniela Carlisi, Carlos Chiesa-Estomba, Antonino Maniaci, Jerome R. Lechien, Miguel Mayo, Nicolas Fakhry and Marianna Lauricella

Cancers 2023, 15(20), 5096; https://doi.org/10.3390/cancers15205096 - 22 Oct 2023

Cited by 3 | Viewed by 1359

Abstract

Laryngeal squamous cell carcinoma (LSCC) is the second most common cancer among head and neck cancers. Despite a lower incidence of laryngeal carcinoma, new diagnostic techniques, and more targeted therapies, the overall survival has not changed significantly in the last decades, leading to [...] Read more.

Laryngeal squamous cell carcinoma (LSCC) is the second most common cancer among head and neck cancers. Despite a lower incidence of laryngeal carcinoma, new diagnostic techniques, and more targeted therapies, the overall survival has not changed significantly in the last decades, leading to a negative prognosis in advanced stages. Recently, several studies have focused on the identification of biomarkers that may play a critical role in the pathogenesis of LSCC. Reviewing the literature on the main databases, this study aims to investigate the role of some biomarkers in LSCC that are correlated with oxidative stress and inflammation: heat shock proteins; metallothioneins; nuclear factor erythroid 2-related factor 2; heme oxygenase; cyclooxygenase-2; and micro ribonucleic acids. This review shows that biomarker expression depends on the type, grade of differentiation, stage, and site of carcinoma. In addition, the role of these biomarkers in LSCC is still little-known and little-studied. However, the study of biomarker expression and the detection of a possible correlation with patients’ epidemiological, clinicopathological, and therapeutics data may lead to better awareness and knowledge of the tumor, to the identification of the best therapeutic strategy, and the most proper follow-up protocol tailored for each patient. In conclusion, the achievement of these goals may improve the prognosis of LSCC patients. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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25 pages, 1678 KiB

Open AccessReview

A Narrative Review on CD44’s Role in Glioblastoma Invasion, Proliferation, and Tumor Recurrence

by Akihiro Inoue, Takanori Ohnishi, Masahiro Nishikawa, Yoshihiro Ohtsuka, Kosuke Kusakabe, Hajime Yano, Junya Tanaka and Takeharu Kunieda

Cancers 2023, 15(19), 4898; https://doi.org/10.3390/cancers15194898 - 09 Oct 2023

Cited by 1 | Viewed by 1307

Abstract

High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in a tumor with inevitable recurrence. GBM recurrence may be caused by glioma stem-like cells (GSCs) that survive many kinds of therapy. GSCs with high expression levels [...] Read more.

High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in a tumor with inevitable recurrence. GBM recurrence may be caused by glioma stem-like cells (GSCs) that survive many kinds of therapy. GSCs with high expression levels of CD44 are highly invasive and resistant to radio-chemotherapy. CD44 is a multifunctional molecule that promotes the invasion and proliferation of tumor cells via various signaling pathways. Among these, paired pathways reciprocally activate invasion and proliferation under different hypoxic conditions. Severe hypoxia (0.5–2.5% O₂) upregulates hypoxia-inducible factor (HIF)-1α, which then activates target genes, including CD44, TGF-β, and cMET, all of which are related to tumor migration and invasion. In contrast, moderate hypoxia (2.5–5% O₂) upregulates HIF-2α, which activates target genes, such as vascular endothelial growth factor (VEGF)/VEGFR2, cMYC, and cyclin D1. All these genes are related to tumor proliferation. Oxygen environments around GBM can change before and after tumor resection. Before resection, the oxygen concentration at the tumor periphery is severely hypoxic. In the reparative stage after resection, the resection cavity shows moderate hypoxia. These observations suggest that upregulated CD44 under severe hypoxia may promote the migration and invasion of tumor cells. Conversely, when tumor resection leads to moderate hypoxia, upregulated HIF-2α activates HIF-2α target genes. The phenotypic transition regulated by CD44, leading to a dichotomy between invasion and proliferation according to hypoxic conditions, may play a crucial role in GBM recurrence. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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27 pages, 5890 KiB

Open AccessReview

The Clinical Validation of Modulated Electro-Hyperthermia (mEHT)

by Sun-Young Lee, Gergo Lorant, Laszlo Grand and Attila Marcell Szasz

Cancers 2023, 15(18), 4569; https://doi.org/10.3390/cancers15184569 - 15 Sep 2023

Cited by 2 | Viewed by 1505

Abstract

The mEHT method uses tissues’ thermal and bioelectromagnetic heterogeneity for the selective mechanisms. The success of the therapy for advanced, relapsed, and metastatic aggressive tumors can only be demonstrated by measuring survival time and quality of life (QoL). The complication is that mEHT-treated [...] Read more.

The mEHT method uses tissues’ thermal and bioelectromagnetic heterogeneity for the selective mechanisms. The success of the therapy for advanced, relapsed, and metastatic aggressive tumors can only be demonstrated by measuring survival time and quality of life (QoL). The complication is that mEHT-treated patients cannot be curatively treated any longer with “gold standards”, where the permanent progression of the disease, the refractory, relapsing situation, the organ failure, the worsening of blood counts, etc., block them. Collecting a cohort of these patients is frequently impossible. Only an intent-to-treat (ITT) patient group was available. Due to the above limitations, many studies have single-arm data collection. The Phase III trial of advanced cervix tumors subgrouping of HIV-negative and -positive patients showed the stable efficacy of mEHT in all patients’ subgroups. The single-arm represents lower-level evidence, which can be improved by comparing the survival data of various studies from different institutes. The Kaplan–Meier probability comparison had no significant differences, so pooled data were compared to other methods. Following this approach, we demonstrate the feasibility and superiority of mEHT in the cases of glioblastoma multiform, pancreas carcinomas, lung tumors, and colorectal tumors. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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15 pages, 1589 KiB

Open AccessReview

The Role of Omentin-1 in Cancers Development and Progression

by Paweł Dec, Agata Poniewierska-Baran, Andrzej Modrzejewski and Andrzej Pawlik

Cancers 2023, 15(15), 3797; https://doi.org/10.3390/cancers15153797 - 26 Jul 2023

Cited by 2 | Viewed by 1154

Abstract

Adipose tissue serves as an energy store and is also an active endocrine organ, exerting activity that influences obesity-related processes through the production of regulatory proteins called adipokines or adipocytokines. Adipokines play important direct and indirect roles in the pathogenesis of insulin resistance, [...] Read more.

Adipose tissue serves as an energy store and is also an active endocrine organ, exerting activity that influences obesity-related processes through the production of regulatory proteins called adipokines or adipocytokines. Adipokines play important direct and indirect roles in the pathogenesis of insulin resistance, the regulation of local and systemic inflammatory processes, and related metabolic complications. There have been an increasing number of studies showing the relationship between some adipokines and carcinogenesis. This work reviews the current literature concerning the effects of omentin-1 on carcinogenesis. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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16 pages, 947 KiB

Open AccessReview

Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option

by Stefano Molica, Constantine Tam, David Allsup and Aaron Polliack

Cancers 2023, 15(14), 3737; https://doi.org/10.3390/cancers15143737 - 23 Jul 2023

Cited by 5 | Viewed by 2615

Abstract

Ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by off-target side effects. Zanubrutinib (zanu) is a second-generation [...] Read more.

Ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by off-target side effects. Zanubrutinib (zanu) is a second-generation BTKi with enhanced target selectivity and occupancy of the kinase binding site. The SEQUOIA study showed that zanu significantly prolonged progression-free survival (PFS) when compared to bendamustine–rituximab (BR) in treatment-naive CLL patients. More recently, data from the phase III ALPINE trial, which directly compared zanu with ibrutinib, demonstrated that zanu’s advantages include an improved safety profile as well as enhanced clinical efficacy. Based on the results of the SEQUOIA and ALPINE pivotal trials, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) licensed zanu for the treatment of patients with CLL or small lymphocytic lymphoma (SLL) in January 2023. The updated (v2.2023) National Comprehensive Cancer Network (NCCN) guidelines and the most recent German CLL algorithm suggest that zanu may replace first-generation BTKis as a preferred therapeutic option for patients with CLL/SLL due to its increased selectivity for the kinase binding site, improved therapeutic efficacy, and favorable toxicity profile. Some drug class-related characteristics such as drug resistance, low complete remission (CR) rates, and indefinite treatment duration still remain with zanu, and the results from recently completed and ongoing fixed-duration clinical trials, combining zanu with an anti-BCL2 agent, are eagerly awaited with the possible promise of a reduced treatment duration and lower financial burden. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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18 pages, 1382 KiB

Open AccessReview

Role of Glucose Metabolic Reprogramming in Breast Cancer Progression and Drug Resistance

by Pan Lei, Wenzhou Wang, Marisela Sheldon, Yutong Sun, Fan Yao and Li Ma

Cancers 2023, 15(13), 3390; https://doi.org/10.3390/cancers15133390 - 28 Jun 2023

Cited by 4 | Viewed by 2195

Abstract

The involvement of glucose metabolic reprogramming in breast cancer progression, metastasis, and therapy resistance has been increasingly appreciated. Studies in recent years have revealed molecular mechanisms by which glucose metabolic reprogramming regulates breast cancer. To date, despite a few metabolism-based drugs being tested [...] Read more.

The involvement of glucose metabolic reprogramming in breast cancer progression, metastasis, and therapy resistance has been increasingly appreciated. Studies in recent years have revealed molecular mechanisms by which glucose metabolic reprogramming regulates breast cancer. To date, despite a few metabolism-based drugs being tested in or en route to clinical trials, no drugs targeting glucose metabolism pathways have yet been approved to treat breast cancer. Here, we review the roles and mechanisms of action of glucose metabolic reprogramming in breast cancer progression and drug resistance. In addition, we summarize the currently available metabolic inhibitors targeting glucose metabolism and discuss the challenges and opportunities in targeting this pathway for breast cancer treatment. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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24 pages, 16503 KiB

Open AccessReview

Early Diagnosis of Oral Cancer: A Complex Polyhedral Problem with a Difficult Solution

by Isabel González-Ruiz, Pablo Ramos-García, Isabel Ruiz-Ávila and Miguel Ángel González-Moles

Cancers 2023, 15(13), 3270; https://doi.org/10.3390/cancers15133270 - 21 Jun 2023

Cited by 6 | Viewed by 11606

Abstract

Oral and oropharyngeal cancers are a growing problem, accounting for 377,713 and 98,412 new cases per year all over the world and 177,757 and 48,143 deaths annually, respectively. Despite the substantial improvement in diagnostic procedures and treatment techniques in recent years, the mortality [...] Read more.

Oral and oropharyngeal cancers are a growing problem, accounting for 377,713 and 98,412 new cases per year all over the world and 177,757 and 48,143 deaths annually, respectively. Despite the substantial improvement in diagnostic procedures and treatment techniques in recent years, the mortality rate has not decreased substantially in the last 40 years, which is still close to 50% of cases. The major cause responsible for this high mortality is associated with the high percentage of oral cancers diagnosed in advanced stages (stages III and IV) where the treatment harbors poor efficacy, resulting in challenges, mutilations, or disability. The main reason for cancer to be diagnosed at an advanced stage is a diagnostic delay, so it is critical to reduce this delay in order to improve the prognosis of patients suffering from oral cancer. The causes of oral cancer diagnostic delay are complex and concern patients, healthcare professionals, and healthcare services. In this manuscript, oral cancer diagnostic delay is critically reviewed based on current evidence, as well as their major causes, main problems, and potential improvement strategies. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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19 pages, 1038 KiB

Open AccessReview

The Role of Microbiota in Pancreatic Cancer

by Valerio Papa, Tommaso Schepis, Gaetano Coppola, Michele Francesco Chiappetta, Livio Enrico Del Vecchio, Tommaso Rozera, Giuseppe Quero, Antonio Gasbarrini, Sergio Alfieri and Alfredo Papa

Cancers 2023, 15(12), 3143; https://doi.org/10.3390/cancers15123143 - 11 Jun 2023

Cited by 5 | Viewed by 2118

Abstract

Pancreatic cancer (PC) has an unfavorable prognosis with few effective therapeutic options. This has led researchers to investigate the possible links between microbiota and PC. A disrupted gut microbiome can lead to chronic inflammation, which is involved in the pathogenesis of PC. In [...] Read more.

Pancreatic cancer (PC) has an unfavorable prognosis with few effective therapeutic options. This has led researchers to investigate the possible links between microbiota and PC. A disrupted gut microbiome can lead to chronic inflammation, which is involved in the pathogenesis of PC. In addition, some bacterial strains can produce carcinogens that promote the growth of cancer cells. Research has also focused on pancreatic and oral microbiota. Changes in these microbiota can contribute to the development and progression of PC. Furthermore, patients with periodontal disease have an increased risk of developing PC. The potential use of microbiota as a prognostic marker or to predict patients’ responses to chemotherapy or immunotherapy is also being explored. Overall, the role of microbiota—including the gut, pancreatic, and oral microbiota—in PC is an active research area. Understanding these associations could lead to new diagnostic and therapeutic targets for this deadly disease. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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16 pages, 515 KiB

Open AccessReview

Preclinical Models of Adrenocortical Cancer

by Andrew J. H. Sedlack, Samual J. Hatfield, Suresh Kumar, Yasuhiro Arakawa, Nitin Roper, Nai-Yun Sun, Naris Nilubol, Katja Kiseljak-Vassiliades, Chuong D. Hoang, Emily K. Bergsland, Jonathan M. Hernandez, Yves Pommier and Jaydira del Rivero

Cancers 2023, 15(11), 2873; https://doi.org/10.3390/cancers15112873 - 23 May 2023

Cited by 4 | Viewed by 1913

Abstract

Adrenocortical cancer is an aggressive endocrine malignancy with an incidence of 0.72 to 1.02 per million people/year, and a very poor prognosis with a five-year survival rate of 22%. As an orphan disease, clinical data are scarce, meaning that drug development and mechanistic [...] Read more.

Adrenocortical cancer is an aggressive endocrine malignancy with an incidence of 0.72 to 1.02 per million people/year, and a very poor prognosis with a five-year survival rate of 22%. As an orphan disease, clinical data are scarce, meaning that drug development and mechanistic research depend especially on preclinical models. While a single human ACC cell line was available for the last three decades, over the last five years, many new in vitro and in vivo preclinical models have been generated. Herein, we review both in vitro (cell lines, spheroids, and organoids) and in vivo (xenograft and genetically engineered mouse) models. Striking leaps have been made in terms of the preclinical models of ACC, and there are now several modern models available publicly and in repositories for research in this area. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

30 pages, 3642 KiB

Open AccessReview

The MAL Family of Proteins: Normal Function, Expression in Cancer, and Potential Use as Cancer Biomarkers

by Leticia Labat-de-Hoz, Armando Rubio-Ramos, Isabel Correas and Miguel A. Alonso

Cancers 2023, 15(10), 2801; https://doi.org/10.3390/cancers15102801 - 17 May 2023

Cited by 3 | Viewed by 1969

Abstract

The MAL family of integral membrane proteins consists of MAL, MAL2, MALL, PLLP, CMTM8, MYADM, and MYADML2. The best characterized members are elements of the machinery that controls specialized pathways of membrane traffic and cell signaling. This review aims to help answer the [...] Read more.

The MAL family of integral membrane proteins consists of MAL, MAL2, MALL, PLLP, CMTM8, MYADM, and MYADML2. The best characterized members are elements of the machinery that controls specialized pathways of membrane traffic and cell signaling. This review aims to help answer the following questions about the MAL-family genes: (i) is their expression regulated in cancer and, if so, how? (ii) What role do they play in cancer? (iii) Might they have biomedical applications? Analysis of large-scale gene expression datasets indicated altered levels of MAL-family transcripts in specific cancer types. A comprehensive literature search provides evidence of MAL-family gene dysregulation and protein function repurposing in cancer. For MAL, and probably for other genes of the family, dysregulation is primarily a consequence of gene methylation, although copy number alterations also contribute to varying degrees. The scrutiny of the two sources of information, datasets and published studies, reveals potential prognostic applications of MAL-family members as cancer biomarkers—for instance, MAL2 in breast cancer, MAL2 and MALL in pancreatic cancer, and MAL and MYADM in lung cancer—and other biomedical uses. The availability of validated antibodies to some MAL-family proteins sanctions their use as cancer biomarkers in routine clinical practice. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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14 pages, 3933 KiB

Open AccessReview

Systematic Review and Meta-Analysis of Oral Anticoagulant Therapy in Atrial Fibrillation Cancer Patients

by Alberto Cereda, Stefano Lucreziotti, Antonio Gabriele Franchina, Alessandra Laricchia, Valentina De Regibus, Barbara Conconi, Matteo Carlà, Andrea Spangaro, Matteo Rocchetti, Luca Ponti, Alessandro Minardi, Elena Sala, Giuseppe Massimo Sangiorgi, Gabriele Tumminello, Lucia Barbieri, Stefano Carugo and Paolo Aseni

Cancers 2023, 15(9), 2574; https://doi.org/10.3390/cancers15092574 - 30 Apr 2023

Cited by 3 | Viewed by 1722

Abstract

(1) Introduction: Cancer and atrial fibrillation (AF) are increasingly coexisting medical challenges. These two conditions share an increased thrombotic and bleeding risk. Although optimal regimens of the most suitable anti-thrombotic therapy are now affirmed in the general population, cancer patients are still particularly [...] Read more.

(1) Introduction: Cancer and atrial fibrillation (AF) are increasingly coexisting medical challenges. These two conditions share an increased thrombotic and bleeding risk. Although optimal regimens of the most suitable anti-thrombotic therapy are now affirmed in the general population, cancer patients are still particularly understudied on the matter; (2) Aims And Methodology: This metanalysis (11 studies (incl. 266,865 patients)) aims at evaluating the ischemic-hemorrhagic risk profile of oncologic patients with AF treated with oral anticoagulants (vitamin K antagonists vs. direct oral anticoagulants); (3) Results: In the oncological population, DOACs confer a benefit in terms of the reduction in ischemic, hemorrhagic and venous thromboembolic events. However, ischemic prevention has a non-insignificant bleeding risk, lower than Warfarin but significant and higher than the non-oncological patients; (4) Conclusions: Anticoagulation with DOACs provides a higher safety profile with respect to VKAs in terms of stroke reduction and a relative bleeding reduction risk. Further studies are needed to better assess the optimal anticoagulation strategy in cancer patients with AF. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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24 pages, 1739 KiB

Open AccessReview

Oncolytic Adenoviruses Armed with Co-Stimulatory Molecules for Cancer Treatment

by Aleksander Gryciuk, Marta Rogalska, Joanna Baran, Lukasz Kuryk and Monika Staniszewska

Cancers 2023, 15(7), 1947; https://doi.org/10.3390/cancers15071947 - 23 Mar 2023

Cited by 5 | Viewed by 1956

Abstract

In clinical trials, adenovirus vectors (AdVs) are commonly used platforms for human gene delivery therapy. High genome capacity and flexibility in gene organization make HAdVs suitable for cloning. Recent advancements in molecular techniques have influenced the development of genetically engineered adenovirus vectors showing [...] Read more.

In clinical trials, adenovirus vectors (AdVs) are commonly used platforms for human gene delivery therapy. High genome capacity and flexibility in gene organization make HAdVs suitable for cloning. Recent advancements in molecular techniques have influenced the development of genetically engineered adenovirus vectors showing therapeutic potential. Increased molecular understanding of the benefits and limitations of HAdVs in preclinical research and clinical studies is a crucial point in the engineering of refined oncolytic vectors. This review presents HAdV species (A–G) used in oncotherapy. We describe the adenovirus genome organizations and modifications, the possibilities oncolytic viruses offer, and their current limitations. Ongoing and ended clinical trials based on oncolytic adenoviruses are presented. This review provides a broad overview of the current knowledge of oncolytic therapy. HAdV-based strategies targeting tumors by employing variable immune modifiers or delivering immune stimulatory factors are of great promise in the field of immune oncologyy This approach can change the face of the fight against cancer, supplying the medical tools to defeat tumors more selectively and safely. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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38 pages, 3288 KiB

Open AccessReview

Targeting Mitochondria with ClpP Agonists as a Novel Therapeutic Opportunity in Breast Cancer

by Rohan Wedam, Yoshimi Endo Greer, David J. Wisniewski, Sarah Weltz, Manjari Kundu, Donna Voeller and Stanley Lipkowitz

Cancers 2023, 15(7), 1936; https://doi.org/10.3390/cancers15071936 - 23 Mar 2023

Cited by 5 | Viewed by 4241

Abstract

Breast cancer is the most frequently diagnosed malignancy worldwide and the leading cause of cancer mortality in women. Despite the recent development of new therapeutics including targeted therapies and immunotherapy, triple-negative breast cancer remains an aggressive form of breast cancer, and thus improved [...] Read more.

Breast cancer is the most frequently diagnosed malignancy worldwide and the leading cause of cancer mortality in women. Despite the recent development of new therapeutics including targeted therapies and immunotherapy, triple-negative breast cancer remains an aggressive form of breast cancer, and thus improved treatments are needed. In recent decades, it has become increasingly clear that breast cancers harbor metabolic plasticity that is controlled by mitochondria. A myriad of studies provide evidence that mitochondria are essential to breast cancer progression. Mitochondria in breast cancers are widely reprogrammed to enhance energy production and biosynthesis of macromolecules required for tumor growth. In this review, we will discuss the current understanding of mitochondrial roles in breast cancers and elucidate why mitochondria are a rational therapeutic target. We will then outline the status of the use of mitochondria-targeting drugs in breast cancers, and highlight ClpP agonists as emerging mitochondria-targeting drugs with a unique mechanism of action. We also illustrate possible drug combination strategies and challenges in the future breast cancer clinic. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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18 pages, 840 KiB

Open AccessReview

Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives

by Alessandro Ottaiano, Mariachiara Santorsola, Luisa Circelli, Anna Maria Trotta, Francesco Izzo, Francesco Perri, Marco Cascella, Francesco Sabbatino, Vincenza Granata, Marco Correra, Luca Tarotto, Salvatore Stilo, Francesco Fiore, Nicola Martucci, Antonello La Rocca, Carmine Picone, Paolo Muto, Valentina Borzillo, Andrea Belli, Renato Patrone, Edoardo Mercadante, Fabiana Tatangelo, Gerardo Ferrara, Annabella Di Mauro, Giosué Scognamiglio, Massimiliano Berretta, Maurizio Capuozzo, Angela Lombardi, Jérôme Galon, Oreste Gualillo, Ugo Pace, Paolo Delrio, Giovanni Savarese, Stefania Scala, Guglielmo Nasti and Michele Caraglia Show full author list Hide full author list

Cancers 2023, 15(6), 1827; https://doi.org/10.3390/cancers15061827 - 17 Mar 2023

Cited by 6 | Viewed by 2134

Abstract

Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as “oligometastatic disease” (OMD). This review discusses new biomarkers, as well as methodological challenges and [...] Read more.

Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as “oligometastatic disease” (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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22 pages, 1833 KiB

Open AccessReview

Modeling Human Brain Tumors and the Microenvironment Using Induced Pluripotent Stem Cells

by Zahraa I. Khamis, Drishty B. Sarker, Yu Xue, Nancy Al-Akkary, Viviana D. James, Changchun Zeng, Yan Li and Qing-Xiang Amy Sang

Cancers 2023, 15(4), 1253; https://doi.org/10.3390/cancers15041253 - 16 Feb 2023

Cited by 4 | Viewed by 2904

Abstract

Brain cancer is a group of diverse and rapidly growing malignancies that originate in the central nervous system (CNS) and have a poor prognosis. The complexity of brain structure and function makes brain cancer modeling extremely difficult, limiting pathological studies and therapeutic developments. [...] Read more.

Brain cancer is a group of diverse and rapidly growing malignancies that originate in the central nervous system (CNS) and have a poor prognosis. The complexity of brain structure and function makes brain cancer modeling extremely difficult, limiting pathological studies and therapeutic developments. Advancements in human pluripotent stem cell technology have opened a window of opportunity for brain cancer modeling, providing a wealth of customizable methods to simulate the disease in vitro. This is achieved with the advent of genome editing and genetic engineering technologies that can simulate germline and somatic mutations found in human brain tumors. This review investigates induced pluripotent stem cell (iPSC)-based approaches to model human brain cancer. The applications of iPSCs as renewable sources of individual brain cell types, brain organoids, blood–brain barrier (BBB), and brain tumor models are discussed. The brain tumor models reviewed are glioblastoma and medulloblastoma. The iPSC-derived isogenic cells and three-dimensional (3D) brain cancer organoids combined with patient-derived xenografts will enhance future compound screening and drug development for these deadly human brain cancers. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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18 pages, 750 KiB

Open AccessSystematic Review

Evaluation of the Cost-Effectiveness of Evidence-Based Interventions to Increase Female Breast and Cervical Cancer Screens: A Systematic Review

by Victoria Phillips, Daniela Franco Montoya and E. Kathleen Adams

Cancers 2024, 16(6), 1134; https://doi.org/10.3390/cancers16061134 - 13 Mar 2024

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Abstract

Purpose: To systematically review published cost-effectiveness analyses of Evidence-Based Interventions (EBIs) recommended by the United States Community Preventive Services Task Force (CPSTF) to increase breast and cervical cancer screening. Methods: We searched PubMed and Embase for prospective cost-effectiveness evaluations of EBIs for breast [...] Read more.

Purpose: To systematically review published cost-effectiveness analyses of Evidence-Based Interventions (EBIs) recommended by the United States Community Preventive Services Task Force (CPSTF) to increase breast and cervical cancer screening. Methods: We searched PubMed and Embase for prospective cost-effectiveness evaluations of EBIs for breast and cervical cancer screening since 1999. We reviewed studies according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and compared the incremental cost-effectiveness ratio (ICERs), defined as cost per additional woman screened, adjusted to 2021 USD, within and across EBIs by cancer type. Results: We identified eleven studies meeting our review criteria: nine were breast cancer-focused, one breast and cervical cancer combined, and one cervical only, which together reported twenty-four cost-effectiveness assessments of outreach programs spanning eight EBIs. One-on-one education programs were the most common EBI evaluated. The average ICER across breast cancer studies was USD 545 (standard deviation [SD] = USD 729.3), while that for cervical cancer studies was USD 197 (SD = 186.6. Provider reminder/recall systems for women already linked to formal care were the most cost-effective, with an average ICERs of USD 41.3 and USD 10.6 for breast and cervical cancer, respectively. Conclusions: Variability in ICERs across and within EBIs reflect the population studied, the specific EBI, and study settings, and was relatively high. ICER estimate uncertainty and the potential for program replicability in other settings and with other populations were not addressed. Given these limitations, using existing cost-effectiveness estimates to inform program funding allocations is not warranted at this time. Additional research is needed on outreach programs for cervical cancer and those which serve minority populations for either of the female cancer screens. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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15 pages, 635 KiB

Open AccessSystematic Review

Serum Paraprotein Is Associated with Adverse Prognostic Factors and Outcome, across Different Subtypes of Mature B-Cell Malignancies—A Systematic Review

by Maria Christina Cox, Fabiana Esposito, Massimiliano Postorino, Adriano Venditti and Arianna Di Napoli

Cancers 2023, 15(18), 4440; https://doi.org/10.3390/cancers15184440 - 06 Sep 2023

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Abstract

The presence of a serum paraprotein (PP) is usually associated with plasma-cell dyscrasias, Waldenstrom Macroglobulinemia/lymphoplasmacytic lymphoma, and cryoglobulinemia. However, PP is also often reported in other high- and low-grade B-cell malignancies. As these reports are sparse and heterogeneous, an overall view on this [...] Read more.

The presence of a serum paraprotein (PP) is usually associated with plasma-cell dyscrasias, Waldenstrom Macroglobulinemia/lymphoplasmacytic lymphoma, and cryoglobulinemia. However, PP is also often reported in other high- and low-grade B-cell malignancies. As these reports are sparse and heterogeneous, an overall view on this topic is lacking, Therefore, we carried out a complete literature review to detail the characteristics, and highlight differences and similarities among lymphoma entities associated with PP. In these settings, IgM and IgG are the prevalent PP subtypes, and their serum concentration is often low or even undetectable without immunofixation. The relevance of paraproteinemia and its prevalence, as well as the impact of IgG vs. IgM PP, seems to differ within B-NHL subtypes and CLL. Nonetheless, paraproteinemia is almost always associated with advanced disease, as well as with immunophenotypic, genetic, and clinical features, impacting prognosis. In fact, PP is reported as an independent prognostic marker of poor outcome. All the above call for implementing clinical practice, with the assessment of paraproteinemia, in patients’ work-up. Indeed, more studies are needed to shed light on the biological mechanism causing more aggressive disease. Furthermore, the significance of paraproteinemia, in the era of targeted therapies, should be assessed in prospective trials. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2023)

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