Recent Advances in Anticancer Strategies

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.7	3.7	2013	15.4 Days	CHF 2600	Submit
Cancers cancers	5.2	7.4	2009	17.9 Days	CHF 2900	Submit
Future Pharmacology futurepharmacol	-	-	2021	20.5 Days	CHF 1000	Submit
Pharmaceutics pharmaceutics	5.4	6.9	2009	14.2 Days	CHF 2900	Submit
Current Oncology curroncol	2.6	2.6	1994	18 Days	CHF 2200	Submit

28 pages, 1776 KiB

Open AccessReview

DNA Damage Responses in Tumors Are Not Proliferative Stimuli, but Rather They Are DNA Repair Actions Requiring Supportive Medical Care

by Zsuzsanna Suba

Cancers 2024, 16(8), 1573; https://doi.org/10.3390/cancers16081573 - 19 Apr 2024

Abstract

Background: In tumors, somatic mutagenesis presumably drives the DNA damage response (DDR) via altered regulatory pathways, increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation-activated DNA repair pathways of tumors.Purpose: Justifying that [...] Read more.

Background: In tumors, somatic mutagenesis presumably drives the DNA damage response (DDR) via altered regulatory pathways, increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation-activated DNA repair pathways of tumors.Purpose: Justifying that cancer cells are not enemies to be killed, but rather that they are ill human cells which have the remnants of physiologic regulatory pathways. Results: 1. Genomic instability and cancer development may be originated from a flaw in estrogen signaling rather than excessive estrogen signaling; 2. Healthy cells with genomic instability exhibit somatic mutations, helping DNA restitution; 3. Somatic mutations in tumor cells aim for the restoration of DNA damage, rather than further genomic derangement; 4. In tumors, estrogen signaling drives the pathways of DNA stabilization, leading to apoptotic death; 5. In peritumoral cellular infiltration, the genomic damage of the tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, an increased growth factor receptor (GFR) signaling confers the unliganded activation of estrogen receptors (ERs); 6. In breast cancer cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signaling and consequential apoptosis. In breast tumors non-responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathways are exhausted, leading to farther genomic instability and unrestrained proliferation. Conclusions: Understanding the real character and behavior of human tumors at the molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy, rather than provoking additional genomic damages. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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18 pages, 2345 KiB

Open AccessSystematic Review

Systematic Review and Meta-Analysis of Laparoscopic versus Robotic-Assisted Surgery for Colon Cancer: Efficacy, Safety, and Outcomes—A Focus on Studies from 2020–2024

by Roxana Loriana Negrut, Adrian Cote, Vasile Aurel Caus and Adrian Marius Maghiar

Cancers 2024, 16(8), 1552; https://doi.org/10.3390/cancers16081552 - 18 Apr 2024

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Abstract

Background: Minimally invasive surgery in the treatment of colon cancer has significantly advanced over the years. This systematic review and meta-analysis aimed to compare the operative outcomes of robotic and laparoscopic surgery in the treatment of colon cancer, focusing on operative time, hospital [...] Read more.

Background: Minimally invasive surgery in the treatment of colon cancer has significantly advanced over the years. This systematic review and meta-analysis aimed to compare the operative outcomes of robotic and laparoscopic surgery in the treatment of colon cancer, focusing on operative time, hospital stay, conversion rates, anastomotic leak rates, and total number lymph node harvested. Methods: Following PRISMA guidelines, we conducted a systematic search across four databases up to January 2024, registering our protocol with PROSPERO (CRD42024513326). We included studies comparing robotic and laparoscopic surgeries for colon cancer, assessing operative time, hospital length of stay, and other perioperative outcomes. Risk of bias was evaluated using the JBI Critical Appraisal Checklist. Statistical analysis utilized a mix of fixed and random-effects models based on heterogeneity. Results: A total of 21 studies met the inclusion criteria, encompassing 50,771 patients, with 21.75% undergoing robotic surgery and 78.25% laparoscopic surgery. Robotic surgery was associated with longer operative times (SMD = −1.27, p < 0.00001) but shorter hospital stays (MD = 0.42, p = 0.003) compared to laparoscopic surgery. Conversion rates were significantly higher in laparoscopic procedures (OR = 2.02, p < 0.00001). No significant differences were found in anastomotic leak rates. A higher number of lymph nodes was harvested by robotic approach (MD = −0.65, p = 0.04). Publication bias was addressed through funnel plot analysis and Egger’s test, indicating the presence of asymmetry (p = 0.006). Conclusions: The choice of surgical method should be individualized, considering factors such as surgeon expertise, medical facilities, and patient-specific considerations. Future research should aim to elucidate long-term outcomes to further guide the clinical decision-making. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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17 pages, 2995 KiB

Open AccessArticle

Glucose Metabolism as a Potential Therapeutic Target in Cytarabine-Resistant Acute Myeloid Leukemia

by Joana Pereira-Vieira, Daniela D. Weber, Sâmia Silva, Catarina Barbosa-Matos, Sara Granja, Rui Manuel Reis, Odília Queirós, Young H. Ko, Barbara Kofler, Margarida Casal and Fátima Baltazar

Pharmaceutics 2024, 16(4), 442; https://doi.org/10.3390/pharmaceutics16040442 - 22 Mar 2024

Viewed by 598

Abstract

Altered glycolytic metabolism has been associated with chemoresistance in acute myeloid leukemia (AML). However, there are still aspects that need clarification, as well as how to explore these metabolic alterations in therapy. In the present study, we aimed to elucidate the role of [...] Read more.

Altered glycolytic metabolism has been associated with chemoresistance in acute myeloid leukemia (AML). However, there are still aspects that need clarification, as well as how to explore these metabolic alterations in therapy. In the present study, we aimed to elucidate the role of glucose metabolism in the acquired resistance of AML cells to cytarabine (Ara-C) and to explore it as a therapeutic target. Resistance was induced by stepwise exposure of AML cells to increasing concentrations of Ara-C. Ara-C-resistant cells were characterized for their growth capacity, genetic alterations, metabolic profile, and sensitivity to different metabolic inhibitors. Ara-C-resistant AML cell lines, KG-1 Ara-R, and MOLM13 Ara-R presented different metabolic profiles. KG-1 Ara-R cells exhibited a more pronounced glycolytic phenotype than parental cells, with a weaker acute response to 3-bromopyruvate (3-BP) but higher sensitivity after 48 h. KG-1 Ara-R cells also display increased respiration rates and are more sensitive to phenformin than parental cells. On the other hand, MOLM13 Ara-R cells display a glucose metabolism profile similar to parental cells, as well as sensitivity to glycolytic inhibitors. These results indicate that acquired resistance to Ara-C in AML may involve metabolic adaptations, which can be explored therapeutically in the AML patient setting who developed resistance to therapy. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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19 pages, 2083 KiB

Open AccessSystematic Review

Intraoperative Techniques That Define the Mucosal Margins of Oral Cancer In-Vivo: A Systematic Review

by Klijs J. de Koning, Carleen M. E. M. Adriaansens, Rob Noorlag, Remco de Bree and Robert J. J. van Es

Cancers 2024, 16(6), 1148; https://doi.org/10.3390/cancers16061148 - 14 Mar 2024

Viewed by 509

Abstract

Background: This systematic review investigates techniques for determining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). The primary treatment involves surgical removal with ≥5 mm margins, highlighting the importance of accurate differentiation between SCC and dysplasia during surgery. Methods: [...] Read more.

Background: This systematic review investigates techniques for determining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). The primary treatment involves surgical removal with ≥5 mm margins, highlighting the importance of accurate differentiation between SCC and dysplasia during surgery. Methods: A comprehensive Embase and PubMed literature search was performed. Studies underwent quality assessment using QUADAS-2. Results: After the full-text screening and exclusion of studies exhibiting high bias, eight studies were included, focusing on three margin visualization techniques: autofluorescence, iodine staining, and narrow-band imaging (NBI). Negative predictive value (NPV) was calculable across the studies, though reference standards varied. Results indicated NPVs for autofluorescence, iodine, and NBI ranging from 61% to 100%, 92% to 99%, and 86% to 100%, respectively. Autofluorescence did not significantly enhance margins compared to white light-guided surgery, while iodine staining demonstrated improvement for mild or moderate dysplasia. NBI lacked comparison with a white light-guided surgery cohort. Conclusions: We recommend studying and comparing the diagnostic accuracy of iodine staining and NBI in larger cohorts of patients with oral SCC, focusing on discriminating between SCC and (severe) dysplasia. Furthermore, we advise reporting the diagnostic accuracy alongside the treatment effects to improve the assessment of these techniques. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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16 pages, 1007 KiB

Open AccessReview

¹⁷⁷Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice

by Kim N. Chi, Steven M. Yip, Glenn Bauman, Stephan Probst, Urban Emmenegger, Christian K. Kollmannsberger, Patrick Martineau, Tamim Niazi, Frédéric Pouliot, Ricardo Rendon, Sebastien J. Hotte, David T. Laidley and Fred Saad

Curr. Oncol. 2024, 31(3), 1400-1415; https://doi.org/10.3390/curroncol31030106 - 07 Mar 2024

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Abstract

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (¹⁷⁷Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a [...] Read more.

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (¹⁷⁷Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of ¹⁷⁷Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of ¹⁷⁷Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of ¹⁷⁷Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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23 pages, 4819 KiB

Open AccessArticle

New MoS₂/Tegafur-Containing Pharmaceutical Formulations for Selective LED-Based Skin Cancer Photo-Chemotherapy

by Miguel T. Campos, Filipa A. L. S. Silva, José Ramiro Fernandes, Susana G. Santos, Fernão D. Magalhães, Maria J. Oliveira and Artur M. Pinto

Pharmaceutics 2024, 16(3), 360; https://doi.org/10.3390/pharmaceutics16030360 - 04 Mar 2024

Viewed by 881

Abstract

Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic [...] Read more.

Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic to healthy tissues; therefore, new, alternative, selective treatments are needed. In this work, a combined photothermal and chemotherapeutic approach is proposed. MoS₂ was used as photothermal agent. It was prepared by a liquid-phase exfoliation and intercalation method using polyvinylpyrrolidone (PVP), followed by recirculation through a custom-built high-power ultrasonication probe. After 6 h of ultrasonication treatment, the average particle size was 165 ± 170 nm. Near-infrared (NIR) irradiation assays (810 nm, 0.1 W/cm², 30 min, 180 J/cm²) confirmed that MoS₂ nanosheets can efficiently convert NIR light into heat and reach 52 °C. The therapeutic doses of MoS₂ (125 µg/mL) and Tegafur (50 µg/mL) were optimized and both were simultaneously incorporated into a Carbopol hydrogel. The cells were brought into contact with the hydrogel and irradiated with a custom-built NIR LED system. In HFF-1 cells (normal human fibroblasts), the metabolic activity was 78% (above the 70% toxicity limit—ISO 10993-5:2009(E)), while in A-431 skin cancer cells, it was 28%. In addition, the MoS₂ + Tegafur hydrogels led to a 1.9-fold decrease in A-431 cancer cell metabolic activity, 72 h after irradiation, in comparison to MoS₂ hydrogels, indicating a combined effect of photothermal and chemotherapy. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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10 pages, 770 KiB

Open AccessArticle

Prognostic Impact of Histologic Subtype and Divergent Differentiation in Patients with Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multicenter Retrospective Study

by Akinori Minato, Nobuki Furubayashi, Yujiro Nagata, Toshihisa Tomoda, Hiroyuki Masaoka, Yoohyun Song, Yoshifumi Hori, Keijiro Kiyoshima, Takahito Negishi, Kentaro Kuroiwa, Narihito Seki, Ikko Tomisaki, Kenichi Harada, Motonobu Nakamura and Naohiro Fujimoto

Curr. Oncol. 2024, 31(2), 862-871; https://doi.org/10.3390/curroncol31020064 - 03 Feb 2024

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Abstract

Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of [...] Read more.

Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of patients with SUC treated with EV for metastatic disease. We retrospectively evaluated consecutive patients with advanced lower and upper urinary tract cancer who received EV after platinum-based chemotherapy and immune checkpoint blockade therapy at six institutions. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with SUC. We identified 44 and 18 patients with PUC and SUC, respectively. Squamous differentiation was the most common subtype element, followed by glandular differentiation and sarcomatoid subtype. Although patients with SUC had a comparable ORR to those with PUC, the duration of response for SUC was short. Patients with SUC had poorer PFS than those with PUC; however, no significant difference was observed in OS. Multivariate analysis revealed that SUC was significantly associated with shorter PFS. Although the response of metastatic SUC to EV was similar to that of PUC, SUC showed faster progression than PUC. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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21 pages, 4725 KiB

Open AccessArticle

Maximizing Anticancer Response with MPS1 and CENPE Inhibition Alongside Apoptosis Induction

by Bárbara Pinto, João P. N. Silva, Patrícia M. A. Silva, Daniel José Barbosa, Bruno Sarmento, Juliana Carvalho Tavares and Hassan Bousbaa

Pharmaceutics 2024, 16(1), 56; https://doi.org/10.3390/pharmaceutics16010056 - 29 Dec 2023

Viewed by 1075

Abstract

Antimitotic compounds, targeting key spindle assembly checkpoint (SAC) components (e.g., MPS1, Aurora kinase B, PLK1, KLP1, CENPE), are potential alternatives to microtubule-targeting antimitotic agents (e.g., paclitaxel) to circumvent resistance and side effects associated with their use. They can be classified into mitotic blockers, [...] Read more.

Antimitotic compounds, targeting key spindle assembly checkpoint (SAC) components (e.g., MPS1, Aurora kinase B, PLK1, KLP1, CENPE), are potential alternatives to microtubule-targeting antimitotic agents (e.g., paclitaxel) to circumvent resistance and side effects associated with their use. They can be classified into mitotic blockers, causing SAC-induced mitotic arrest, or mitotic drivers, pushing cells through aberrant mitosis by overriding SAC. These drugs, although advancing to clinical trials, exhibit unsatisfactory cancer treatment outcomes as monotherapy, probably due to variable cell fate responses driven by cyclin B degradation and apoptosis signal accumulation networks. We investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic navitoclax in lung cancer cells treated with the selective CENPE inhibitor GSK923295 (mitotic blocker) or the MPS1 inhibitor BAY1217389 (mitotic driver). Our aim was to steer treated cancer cells towards cell death. BH3-mimetics, in combination with both mitotic blockers and drivers, induced substantial cell death, mainly through apoptosis, in 2D and 3D cultures. Crucially, these synergistic concentrations were less toxic to non-tumor cells. This highlights the significance of combining BH3-mimetics with antimitotics, either blockers or drivers, which have reached the clinical trial phase, to enhance their effectiveness. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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9 pages, 554 KiB

Open AccessArticle

IGF1 and Insulin Receptor Single Nucleotide Variants Associated with Response in HER2-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy with or without a Fasting Mimicking Diet (BOOG 2013-04 DIRECT Trial)

by Nadia de Gruil, Stefan Böhringer, Stefanie de Groot, Hanno Pijl, Judith R. Kroep and Jesse J. Swen

Cancers 2023, 15(24), 5872; https://doi.org/10.3390/cancers15245872 - 17 Dec 2023

Viewed by 790

Abstract

Aim: We aimed to investigate associations between IGF1R and INSR single nucleotide variants (SNVs) and clinical response in patients with breast cancer treated with neoadjuvant chemotherapy with or without a fasting mimicking diet (FMD) from the DIRECT trial (NCT02126449), since insulin-like growth factor [...] Read more.

Aim: We aimed to investigate associations between IGF1R and INSR single nucleotide variants (SNVs) and clinical response in patients with breast cancer treated with neoadjuvant chemotherapy with or without a fasting mimicking diet (FMD) from the DIRECT trial (NCT02126449), since insulin-like growth factor 1 (IGF1) and the insulin pathway are heavily involved in tumor growth and progression. Methods: Germline DNA from 113 patients was tested for 17 systematically selected candidate SNVs in IGF1R and INSR with pathological and radiological response. Results: IGF1R variants A > G (rs3743259) and G > A (rs3743258) are associated with worse pathological response compared to reference alleles p = 0.002, OR = 0.42 (95%CI: 0.24; 0.73); p = 0.0016; OR = 0.40 (95%CI: 0.23; 0.70). INSR T > C (rs1051690) may be associated with worse radiological response p = 0.02, OR = 2.92 (95%CI: 1.16; 7.36), although not significant after Bonferroni correction. Exploratory interaction analysis suggests that IGF1R SNVs rs2684787 and rs2654980 interact negatively with the FMD group regarding radiological response p = 0.036, OR = 5.13 (95%CI: 1.12; 23.63); p = 0.024, OR = 5.71 (95%CI: 1.26; 25.85). Conclusions: The IGF1R variants rs3743259 and rs3743258 are negatively associated with pathological response in this cohort, suggesting potential relevance as a predictive biomarker. Further research is needed to validate these findings and elucidate the underlying mechanisms and interaction with FMD. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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14 pages, 656 KiB

Open AccessSystematic Review

Combination of Local Ablative Techniques with Radiotherapy for Primary and Recurrent Lung Cancer: A Systematic Review

by Paolo Bonome, Donato Pezzulla, Valentina Lancellotta, Anna Rita Scrofani, Gabriella Macchia, Elena Rodolfino, Luca Tagliaferri, György Kovács, Francesco Deodato and Roberto Iezzi

Cancers 2023, 15(24), 5869; https://doi.org/10.3390/cancers15245869 - 16 Dec 2023

Viewed by 713

Abstract

In patients with early-stage or recurrent NSCLC who are unable to tolerate surgery, a benefit could derive only from a systemic therapy or another few forms of local therapy. A systematic review was performed to evaluate the feasibility and the effectiveness of radiotherapy [...] Read more.

In patients with early-stage or recurrent NSCLC who are unable to tolerate surgery, a benefit could derive only from a systemic therapy or another few forms of local therapy. A systematic review was performed to evaluate the feasibility and the effectiveness of radiotherapy combined with local ablative therapies in the treatment of primary and recurrent lung cancer in terms of toxicity profile and local control rate. Six studies featuring a total of 115 patients who met eligibility criteria and 119 lesions were included. Three studies evaluated lung cancer patients with a medically inoperable condition treated with image-guided local ablative therapies followed by radiotherapy: their local control rate (LC) ranged from 75% to 91.7% with only 15 patients (19.4%) reporting local recurrence after combined modality treatment. The other three studies provided a salvage option for patients with locally recurrent NSCLC after RT: the median follow-up period varied from 8.3 to 69.3 months with an LC rate ranging from 50% to 100%. The most common complications were radiation pneumonitis (9.5%) and pneumothorax (29.8%). The proposed intervention appears to be promising in terms of toxicity profile and local control rate. Further prospective studies are need to better delineate combining LTA-RT treatment benefits in this setting. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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18 pages, 1451 KiB

Open AccessReview

Navigating the Immune Maze: Pioneering Strategies for Unshackling Cancer Immunotherapy Resistance

by Liqin Yao, Qingqing Wang and Wenxue Ma

Cancers 2023, 15(24), 5857; https://doi.org/10.3390/cancers15245857 - 15 Dec 2023

Cited by 1 | Viewed by 928

Abstract

Cancer immunotherapy has ushered in a transformative era in oncology, offering unprecedented promise and opportunities. Despite its remarkable breakthroughs, the field continues to grapple with the persistent challenge of treatment resistance. This resistance not only undermines the widespread efficacy of these pioneering treatments, [...] Read more.

Cancer immunotherapy has ushered in a transformative era in oncology, offering unprecedented promise and opportunities. Despite its remarkable breakthroughs, the field continues to grapple with the persistent challenge of treatment resistance. This resistance not only undermines the widespread efficacy of these pioneering treatments, but also underscores the pressing need for further research. Our exploration into the intricate realm of cancer immunotherapy resistance reveals various mechanisms at play, from primary and secondary resistance to the significant impact of genetic and epigenetic factors, as well as the crucial role of the tumor microenvironment (TME). Furthermore, we stress the importance of devising innovative strategies to counteract this resistance, such as employing combination therapies, tailoring immune checkpoints, and implementing real-time monitoring. By championing these state-of-the-art methods, we anticipate a paradigm that blends personalized healthcare with improved treatment options and is firmly committed to patient welfare. Through a comprehensive and multifaceted approach, we strive to tackle the challenges of resistance, aspiring to elevate cancer immunotherapy as a beacon of hope for patients around the world. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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17 pages, 1471 KiB

Open AccessReview

Colorectal Cancer Stem Cells and Targeted Agents

by Haobin Zhao, Ruining Han, Zhankun Wang, Junfang Xian and Xiaosu Bai

Pharmaceutics 2023, 15(12), 2763; https://doi.org/10.3390/pharmaceutics15122763 - 12 Dec 2023

Viewed by 1270

Abstract

Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to [...] Read more.

Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to eliminate. Colorectal cancer is the third-most common cancer and the second leading cause of cancer death worldwide. Targeting colorectal cancer stem cells (CR-CSCs) can inhibit colorectal cancer metastasis, enhance therapeutic efficacy and reduce recurrence. Here, we introduced the origin, biomarker proteins, identification, cultivation and research techniques of CR-CSCs, and we summarized the signaling pathways that regulate the stemness of CR-CSCs, such as Wnt, JAK/STAT3, Notch and Hh signaling pathway. In addition to these, we also reviewed recent anti-CR-CSC drugs targeting signaling pathways, biomarkers and other regulators. These will help researchers gain insight into the current agents targeting to CR-CSCs, explore new cancer drugs and propose potential therapies. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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29 pages, 2646 KiB

Open AccessReview

Targeting Glucose Metabolism in Cancer Cells as an Approach to Overcoming Drug Resistance

by Andrea Cunha, Patrícia M. A. Silva, Bruno Sarmento and Odília Queirós

Pharmaceutics 2023, 15(11), 2610; https://doi.org/10.3390/pharmaceutics15112610 - 10 Nov 2023

Cited by 1 | Viewed by 1951

Abstract

The “Warburg effect” consists of a metabolic shift in energy production from oxidative phosphorylation to glycolysis. The continuous activation of glycolysis in cancer cells causes rapid energy production and an increase in lactate, leading to the acidification of the tumour microenvironment, chemo- and [...] Read more.

The “Warburg effect” consists of a metabolic shift in energy production from oxidative phosphorylation to glycolysis. The continuous activation of glycolysis in cancer cells causes rapid energy production and an increase in lactate, leading to the acidification of the tumour microenvironment, chemo- and radioresistance, as well as poor patient survival. Nevertheless, the mitochondrial metabolism can be also involved in aggressive cancer characteristics. The metabolic differences between cancer and normal tissues can be considered the Achilles heel of cancer, offering a strategy for new therapies. One of the main causes of treatment resistance consists of the increased expression of efflux pumps, and multidrug resistance (MDR) proteins, which are able to export chemotherapeutics out of the cell. Cells expressing MDR proteins require ATP to mediate the efflux of their drug substrates. Thus, inhibition of the main energy-producing pathways in cancer cells, not only induces cancer cell death per se, but also overcomes multidrug resistance. Given that most anticancer drugs do not have the ability to distinguish normal cells from cancer cells, a number of drug delivery systems have been developed. These nanodrug delivery systems provide flexible and effective methods to overcome MDR by facilitating cellular uptake, increasing drug accumulation, reducing drug efflux, improving targeted drug delivery, co-administering synergistic agents, and increasing the half-life of drugs in circulation. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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20 pages, 2401 KiB

Open AccessEditor’s ChoiceReview

The Value of Microbes in Cancer Neoantigen Immunotherapy

by Junrui Tian and Jian Ma

Pharmaceutics 2023, 15(8), 2138; https://doi.org/10.3390/pharmaceutics15082138 - 14 Aug 2023

Viewed by 1286

Abstract

Tumor neoantigens are widely used in cancer immunotherapy, and a growing body of research suggests that microbes play an important role in these neoantigen-based immunotherapeutic processes. The human body and its surrounding environment are filled with a large number of microbes that are [...] Read more.

Tumor neoantigens are widely used in cancer immunotherapy, and a growing body of research suggests that microbes play an important role in these neoantigen-based immunotherapeutic processes. The human body and its surrounding environment are filled with a large number of microbes that are in long-term interaction with the organism. The microbiota can modulate our immune system, help activate neoantigen-reactive T cells, and play a great role in the process of targeting tumor neoantigens for therapy. Recent studies have revealed the interconnection between microbes and neoantigens, which can cross-react with each other through molecular mimicry, providing theoretical guidance for more relevant studies. The current applications of microbes in immunotherapy against tumor neoantigens are mainly focused on cancer vaccine development and immunotherapy with immune checkpoint inhibitors. This article summarizes the related fields and suggests the importance of microbes in immunotherapy against neoantigens. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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44 pages, 2410 KiB

Open AccessReview

The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies

by Hasan Slika, Paolo Alimonti, Divyaansh Raj, Chad Caraway, Safwan Alomari, Eric M. Jackson and Betty Tyler

Cancers 2023, 15(15), 3889; https://doi.org/10.3390/cancers15153889 - 30 Jul 2023

Viewed by 2150

Abstract

Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with [...] Read more.

Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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16 pages, 1760 KiB

Open AccessReview

FLASH Radiotherapy and the Use of Radiation Dosimeters

by Sarkar Siddique, Harry E. Ruda and James C. L. Chow

Cancers 2023, 15(15), 3883; https://doi.org/10.3390/cancers15153883 - 30 Jul 2023

Cited by 5 | Viewed by 2075

Abstract

Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. [...] Read more.

Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. Monte Carlo (MC) simulation is a valuable tool for dose calculation in RT and has been investigated for optimizing FLASH RT. Various MC codes, such as EGSnrc, DOSXYZnrc, and Geant4, have been used to simulate dose distributions and optimize treatment plans. Accurate dosimetry is essential for FLASH RT, and radiation detectors play a crucial role in measuring dose delivery. Solid-state detectors, including diamond detectors such as microDiamond, have demonstrated linear responses and good agreement with reference detectors in UHDR and ultra-high dose per pulse (UHDPP) ranges. Ionization chambers are commonly used for dose measurement, and advancements have been made to address their response nonlinearities at UHDPP. Studies have proposed new calculation methods and empirical models for ion recombination in ionization chambers to improve their accuracy in FLASH RT. Additionally, strip-segmented ionization chamber arrays have shown potential for the experimental measurement of dose rate distribution in proton pencil beam scanning. Radiochromic films, such as Gafchromic^TM EBT3, have been used for absolute dose measurement and to validate MC simulation results in high-energy X-rays, triggering the FLASH effect. These films have been utilized to characterize ionization chambers and measure off-axis and depth dose distributions in FLASH RT. In conclusion, MC simulation provides accurate dose calculation and optimization for FLASH RT, while radiation detectors, including diamond detectors, ionization chambers, and radiochromic films, offer valuable tools for dosimetry in UHDR environments. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of FLASH RT, potentially revolutionizing cancer treatment. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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