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Homologous Recombination Is Associated with Enhanced Anti-Tumor Innate Immunity and Favorable Prognosis in Head and Neck Cancer
Secondary Genetic Events and Their Relationship to TP53 Mutation in Mantle Cell Lymphoma: A Sub-Study from the FIL_MANTLE-FIRST BIO on Behalf of Fondazione Italiana Linfomi (FIL)
The Tumor Environment in Peritoneal Carcinomatosis and Malignant Pleural Effusions: Implications for Therapy

Journal Description

Cancers

Cancers is a peer-reviewed, open access journal of oncology published semimonthly online. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 19.1 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2025).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Sections: published in 18 topical sections.
Companion journals for Cancers include: Radiation and Onco.
Journal Clusters of Oncology: Cancers, Current Oncology, Onco and Targets.

Impact Factor: 4.4 (2024); 5-Year Impact Factor: 4.8 (2024)

Imprint Information Journal Flyer Open Access ISSN: 2072-6694

Latest Articles

14 pages, 467 KB

Open AccessArticle

15-Day Duration of Venetoclax Combined with Azacitidine in Treatment-Naive Higher-Risk Myelodysplastic Syndromes: A Prospective Multicenter Study

by Binbin Lai, Chen Mei, Xiao Yan, Lieguang Chen, Yi Wang, Lixia Sheng, Shanhao Tang, Liping Mao, Ping Zhang, Yongcheng Sun, Wanzhuo Xie, De Zhou, Wenyuan Mai, Huafeng Wang, Liya Ma, Yinjun Lou, Wenjun Wu, Huifang Jiang, Jin Zhang, Baodong Ye, Hongyan Tong and Guifang Ouyang Show full author list Hide full author list

Cancers 2026, 18(1), 159; https://doi.org/10.3390/cancers18010159 (registering DOI) - 2 Jan 2026

Background: Higher-risk myelodysplastic syndromes (HR-MDS) carry a high risk of progression to acute myeloid leukemia and poor overall survival. Hypomethylating agents (HMAs), such as azacitidine, remain the standard of care but have limited efficacy. A 15-day venetoclax-azacitidine regimen has shown promising objective response [...] Read more.

Background: Higher-risk myelodysplastic syndromes (HR-MDS) carry a high risk of progression to acute myeloid leukemia and poor overall survival. Hypomethylating agents (HMAs), such as azacitidine, remain the standard of care but have limited efficacy. A 15-day venetoclax-azacitidine regimen has shown promising objective response rates (ORR) and potential as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT) in relapsed/refractory HR-MDS. We conducted a prospective multicenter trial to evaluate its efficacy and safety in previously untreated patients. Methods: This multicenter prospective study enrolled treatment-naïve HR-MDS patients (IPSS-R > 3.5). Venetoclax was administered on days 1–15 (escalated from 100 to 400 mg), combined with azacitidine (75 mg/m²) on days 1–7 of each 28-day cycle. The primary endpoint was ORR (2006 IWG criteria); secondary endpoints included complete remission (CR), overall survival (OS), and AML progression. Results: Twenty-eight patients (median age: 63 years) were enrolled, with a median follow-up of 8.5 months. ORR was 85.7% per 2006 IWG (CR: 35.7%, marrow CR: 50.0%), and 78.6% per 2023 IWG (CR: 35.7%). Responses were consistent across molecular and IPSS-R subgroups. Median OS was not reached. High neutrophil count and high cytogenetic risk were favorable factors; TP53 mutation/deletion was an adverse prognostic marker. Grade 3–4 hematologic toxicities included neutropenia (96.4%), anemia (71.4%), and thrombocytopenia (64.3%). Serious adverse events (35.7%) were mainly infections. No dose-limiting or unexpected toxicities were observed. Conclusions: The 15-day venetoclax plus azacitidine regimen demonstrated high efficacy and manageable toxicity in treatment-naïve HR-MDS. It may be particularly beneficial for patients with high neutrophil counts, adverse cytogenetics, or those eligible for HSCT, supporting further investigation in larger trials. Full article

(This article belongs to the Section Cancer Therapy)

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21 pages, 328 KB

Open AccessReview

Risk Scores for Stratifying Hepatocellular Carcinoma and Optimizing Surveillance Strategies

by Yu-Ping Chang, Yun-Chu Chen and Chen-Hua Liu

Cancers 2026, 18(1), 158; https://doi.org/10.3390/cancers18010158 (registering DOI) - 2 Jan 2026

Background: Hepatocellular carcinoma (HCC) is a major global health burden, with poor outcomes largely due to diagnosis at an advanced stage and the limited performance of current surveillance tools. Ultrasound with alpha fetoprotein (AFP) provides insufficient sensitivity for early-stage detection, highlighting the need [...] Read more.

Background: Hepatocellular carcinoma (HCC) is a major global health burden, with poor outcomes largely due to diagnosis at an advanced stage and the limited performance of current surveillance tools. Ultrasound with alpha fetoprotein (AFP) provides insufficient sensitivity for early-stage detection, highlighting the need to better identify the at-risk population. Focus of the review: Many HCC risk scores have been proposed; however, some depend on specialized laboratory data that are not widely available. This review summarizes risk scores that show reliable discrimination and rely on demographic, clinical, or molecular information that can be readily obtained in routine care. Conclusions: Advances in HCC risk scores support the move toward surveillance approaches based on individual risk. These tools can improve risk stratification, increase the likelihood of early detection, and potentially support better outcomes for people who belong to the at-risk population for HCC. Full article

(This article belongs to the Special Issue Prevention, Early Detection, and Surgical Oncology in Hepatocellular Carcinoma, Pancreatic Cancer, and Gastrointestinal Cancer)

28 pages, 4974 KB

Open AccessArticle

Global Patterns and Temporal Trends in Ovarian and Uterine Cancer Mortality Attributable to High Body-Mass Index, 1990–2023

by Irena Ilic, Vladimir Jakovljevic, Srdjan Lazic and Milena Ilic

Cancers 2026, 18(1), 157; https://doi.org/10.3390/cancers18010157 (registering DOI) - 2 Jan 2026

Background/Objectives: The risk factors for ovarian and uterine cancer remain insufficiently known. This study aimed to assess global trends in mortality from ovarian and uterine cancer attributable to high body-mass index (BMI) in 1990–2023. Methods: An observational epidemiological study was conducted. [...] Read more.

Background/Objectives: The risk factors for ovarian and uterine cancer remain insufficiently known. This study aimed to assess global trends in mortality from ovarian and uterine cancer attributable to high body-mass index (BMI) in 1990–2023. Methods: An observational epidemiological study was conducted. The age-standardized rates (ASRs) of mortality were retrieved from the Global Burden of Disease study. Trends were evaluated using joinpoint analysis. The Average Annual Percentage Change (AAPC, %), with a 95% Confidence Interval (CI), was calculated. Results: Globally, the trend in ASRs of ovarian cancer deaths attributable to high BMI increased significantly (AAPC = +0.4%, 95% CI = 0.3 to 0.5). The growth trend in South Asia (AAPC = +8.7%, 95% CI = 8.1 to 9.2) was 30 times greater than in Eastern Europe (AAPC = +0.3%, 95% CI = 0.1 to 0.5). Declining trends in mortality from ovarian cancer were observed only in Australasia (AAPC = −0.2%, 95% CI = −0.4 to −0.1), High-income North America (AAPC = −0.3%, 95% CI = −0.6 to −0.0), and Western Europe (AAPC = −0.7%, 95% CI = −0.8 to −0.6). For uterine cancer, the global trend of mortality also increased (AAPC = +0.1, 95% CI = 0.0 to 0.2), with the trend growing fastest in South Asia (AAPC = +4.2%, 95% CI = 4.0 to 4.4). Decreasing trends in mortality from uterine cancer due to high BMI were observed only in Central Asia (AAPC = −0.6%, 95% CI = −0.9 to −0.4), East Asia (AAPC = −2.2%, 95% CI = −2.6 to −1.8), and Southern Latin America (AAPC = −0.4%, 95% CI = −0.6 to −0.1). Additionally, an accelerated increase in mortality trends for both ovarian and uterine cancer attributable to high BMI was observed in 2020–2023, which corresponds to the period of the COVID-19 pandemic. Conclusions: Further analytical epidemiological studies are required to clarify the relationship between ovarian and uterine cancer and high BMI. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

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29 pages, 1038 KB

Open AccessReview

Targeting the MAPK Pathway in Brain Tumors: Mechanisms and Therapeutic Opportunities

by Dimitrios Vrachas, Elisavet Kosma, Angeliki-Ioanna Giannopoulou, Angeliki Margoni, Antonios N. Gargalionis, Elias A. El-Habr, Christina Piperi and Christos Adamopoulos

Cancers 2026, 18(1), 156; https://doi.org/10.3390/cancers18010156 (registering DOI) - 2 Jan 2026

Central nervous system (CNS) tumors consist of a diverse set of malignancies that remain clinically challenging due to their biological complexity, high morbidity, and limited responsiveness to current therapies. A growing body of genomic evidence has revealed that dysregulation of the mitogen-activated protein [...] Read more.

Central nervous system (CNS) tumors consist of a diverse set of malignancies that remain clinically challenging due to their biological complexity, high morbidity, and limited responsiveness to current therapies. A growing body of genomic evidence has revealed that dysregulation of the mitogen-activated protein kinase (MAPK) signaling pathway is a recurrent and unifying characteristic across many pediatric and adult CNS tumor entities. Alterations affecting upstream receptor tyrosine kinases (RTKs), RAS GTPases, RAF kinases, and other associated regulators contribute to MAPK signaling pathway hyperactivation, shaping tumor behavior, therapy response and resistance. These aberrations ranging from hotspot mutations such as BRAF V600E and oncogenic fusions like BRAF–KIAA1549 are particularly enriched in gliomas and glioneuronal tumors, highlighting MAPK signaling as a key oncogenic driver. The expanding availability of molecularly targeted compounds, including selective inhibitors of RAF, MEK and ERK, has begun to transform treatment approaches for specific molecular subtypes. However, the clinical benefit of MAPK-directed therapies is frequently limited by restricted blood–brain barrier (BBB) penetration, intratumoral heterogeneity, parallel pathway reactivation, and an immunosuppressive tumor microenvironment (TME). In this review, we synthesize current knowledge on MAPK pathway alterations in CNS tumors and evaluate the therapeutic landscape of MAPK inhibition, with emphasis on approved agents, emerging compounds, combination strategies, and novel drug-delivery technologies. We also discuss mechanisms that undermine treatment efficacy and highlight future directions aimed at integrating MAPK-targeted therapy into precision-based management of brain tumors. Full article

(This article belongs to the Special Issue Insights from the Editorial Board Member)

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15 pages, 3636 KB

Open AccessArticle

Three-Year Outcomes of Neoadjuvant Chemoimmunotherapy vs. Neoadjuvant Chemoradiotherapy in Resectable Esophageal Cancer: A Multicenter Retrospective Study

by Shilong Deng, Xue Yan, Ying Peng, Lijun Zhu, Yongshi Shen, Wenmin Ying, Yuanji Xu and Zhichao Fu

Cancers 2026, 18(1), 155; https://doi.org/10.3390/cancers18010155 (registering DOI) - 1 Jan 2026

Background: Patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) have poor prognosis after surgery. Neoadjuvant chemoimmunotherapy (nCIT) and neoadjuvant chemoradiotherapy (nCRT) may improve outcomes, but their long-term efficacy remains unclear. Methods: This multicenter study analyzed LA-ESCC patients from three Chinese [...] Read more.

Background: Patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) have poor prognosis after surgery. Neoadjuvant chemoimmunotherapy (nCIT) and neoadjuvant chemoradiotherapy (nCRT) may improve outcomes, but their long-term efficacy remains unclear. Methods: This multicenter study analyzed LA-ESCC patients from three Chinese hospitals (2015–2024) who received nCIT or nCRT followed by surgery. Primary endpoint was 3-year overall survival (OS); secondary endpoints included objective response rate (ORR), pathologic complete response (pCR), disease-free survival (DFS), and adverse events. Propensity score matching balanced baseline characteristics. Results: Among 225 patients (87 nCRT, 138 nCIT), matched cohorts (87 per group) showed that nCRT had higher ORR (85.06% vs. 45.98%), T/N downstaging rates (78.16% vs. 58.62%; 85.06% vs. 45.98%), and pCR (37.90% vs. 14.90%) (all p < 0.01). After median follow-up (nCIT: 44.5 months; nCRT: 35.1 months), nCIT improved 3-year OS (75.90% vs. 55.60%) and DFS (66.40% vs. 47.30%) (p < 0.05). Subgroup analysis favored nCRT in N+ or non-cT4 disease. Clinical N stage independently predicted survival. Conclusion: nCIT demonstrates superior survival benefits in LA-ESCC, while nCRT may be more effective for N+ or non-cT4 patients. Further randomized trials are warranted. Full article

(This article belongs to the Section Cancer Therapy)

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20 pages, 3029 KB

Open AccessArticle

Computer-Assisted Intraoperative Navigation in Pediatric Head and Neck Surgical Oncology: A Single-Center Case Series and Scoping Review of the Literature

by Jordan Whittles, Ajay Bharathan, Shannon Hall, James Baumgartner and Joseph Lopez

Cancers 2026, 18(1), 154; https://doi.org/10.3390/cancers18010154 (registering DOI) - 1 Jan 2026

Background: As pediatric head and neck cancer (pHNC) incidence increases, the development of new surgical oncology techniques to reduce morbidity are essential. Intraoperative navigation (iNav) represents the most translatable technology among both the model-comparative and integrative surgical navigation technologies to optimize surgical outcomes. [...] Read more.

Background: As pediatric head and neck cancer (pHNC) incidence increases, the development of new surgical oncology techniques to reduce morbidity are essential. Intraoperative navigation (iNav) represents the most translatable technology among both the model-comparative and integrative surgical navigation technologies to optimize surgical outcomes. Methods: A scoping review of the literature was performed according to PRISMA guidelines from 1970 to present (February 2025), investigating the use of iNav in cases of pHNC. Patient case details and authors’ perception of iNav’s utility were analyzed. A single-center retrospective case series review (September 2022 to September 2025) of the senior authors’ experience employing iNav in pHNC cases was also performed. Results: The scoping review identified twenty-seven cases of pHNC from sixteen studies that both utilized iNav and met the inclusion criteria. Many of the authors commented favorably on the utility of iNav technology, while concurrently agreeing upon its limitations. The case series review identified five cases of pHNC that met the inclusion criteria. This small case series revealed a 100% R0 resection rate with the use of iNav in four pHNC resections. The fifth case used iNav for biopsy site selection. Conclusions: The results of our scoping review as well as our institutional experience with this technology demonstrate its utility in guiding surgical approach, confirming depth of resection, and navigating marginal assessment. This study was limited by incidental and incomplete reporting of iNav’s clinical application to pHNC; several extensive institutional reports had to be excluded due to insufficiently detailed data linkage. Our review builds upon the existing pediatric surgical literature, anchoring the evidentiary justification for the application of iNav to pediatric head and neck surgery. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Pediatric Solid Tumors)

15 pages, 3966 KB

Open AccessArticle

Diagnostic Performance of Line-Field Confocal Optical Coherence Tomography for Basal Cell Carcinoma: A Prospective Study

by Carmen Orte Cano, Dilara Sanak, Clément Lenoir, Gwendoline Diet, Margot Fontaine, Lucas Boussingault, Lyna Mtimet, Dina Aktas, Stefan Rusu, Anne-Laure Trepant, Gerardo Palmisano, Alessandro Di Stefani, Elisa Cinotti, Linda Tognetti, Javiera Pérez-Anker, Ketty Peris, Pietro Rubegni, Susana Puig, Josep Malvehy, Jean-Luc Perrot, Véronique Del Marmol and Mariano Suppa Show full author list Hide full author list

Cancers 2026, 18(1), 153; https://doi.org/10.3390/cancers18010153 (registering DOI) - 1 Jan 2026

Background: Line-field confocal optical coherence tomography (LC-OCT) is an innovative non-invasive imaging technique recently introduced in dermatology. Its use has been established particularly in the diagnosis of skin cancer. The LC-OCT description of basal cell carcinoma (BCC) criteria has served for the [...] Read more.

Background: Line-field confocal optical coherence tomography (LC-OCT) is an innovative non-invasive imaging technique recently introduced in dermatology. Its use has been established particularly in the diagnosis of skin cancer. The LC-OCT description of basal cell carcinoma (BCC) criteria has served for the conduction of retrospective evaluations on its diagnostic performance, which demonstrated its utility in diagnosis and subtyping BCC. However, prospective studies performed at patients’ bedside are currently lacking in this field. Objective: The objective of the study was to provide parameters of LC-OCT diagnostic performance for BCC derived from a prospective study performed at patients’ bedside. Methods: Lesions clinically equivocal for BCC were prospectively included. Dermoscopic and LC-OCT diagnoses were obtained at the patients’ bedside by an expert observer prior to surgical excision or biopsy. Results: A total of 214 lesions (163 BCCs and 51 BCC imitators) belonging to 119 patients were included. For the differentiation of BCC from BCC-imitators, LC-OCT had the same sensitivity as dermoscopy (98%) but a better specificity (90% vs. 37%). For the discrimination of superficial BCC from other BCC subtypes, LC-OCT had an increased sensitivity and specificity compared to dermoscopy (72% vs. 62%, and 97% vs. 84%, respectively). Conclusions: This prospective study showed that the diagnostic performance for BCC diagnosis and subtyping can be remarkedly increased by LC-OCT compared to dermoscopic examination alone. Our data encourages the inclusion of LC-OCT in the diagnostic process and management of equivocal lesions for BCC. Full article

(This article belongs to the Special Issue Skin Cancer Prevention: Strategies, Challenges and Future Directions)

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20 pages, 1407 KB

Open AccessArticle

Prediction Model of Lymph Node Metastasis in Cervical Cancer Based on MRI Habitat Radiomics

by Mei Wang, Yu Cao, Weiwei Zhang, Yun Liang, Jizhao Liu and Junqiang Lei

Cancers 2026, 18(1), 152; https://doi.org/10.3390/cancers18010152 - 31 Dec 2025

Background: Radiomics provides a non-invasive approach for predicting lymph node metastasis (LNM) in cervical cancer, but conventional whole-tumor analysis often overlooks intratumoral heterogeneity. Methods: This study aimed to develop and validate an MRI-based habitat radiomics model for preoperative prediction of pelvic [...] Read more.

Background: Radiomics provides a non-invasive approach for predicting lymph node metastasis (LNM) in cervical cancer, but conventional whole-tumor analysis often overlooks intratumoral heterogeneity. Methods: This study aimed to develop and validate an MRI-based habitat radiomics model for preoperative prediction of pelvic LNM in early-stage cervical cancer. Tumor regions were delineated on diffusion-weighted imaging, and intratumoral habitats were generated using unsupervised K-means clustering. Radiomic features were extracted from whole tumors and habitat subregions, combined with clinical variables, and selected using correlation analysis and LASSO regression. Four models—clinical, conventional radiomics, habitat radiomics, and combined—were constructed and evaluated. Results: In internal validation, the combined model achieved the best performance (AUC = 0.895), outperforming the clinical (AUC = 0.799), conventional radiomics (AUC = 0.611), and habitat models (AUC = 0.872). Calibration and decision curve analyses demonstrated good agreement and clinical utility. Conclusions: Integrating habitat-based radiomics with clinical factors significantly improves the preoperative prediction of LNM, providing a robust and clinically applicable tool for individualized management of cervical cancer patients. Full article

(This article belongs to the Section Methods and Technologies Development)

40 pages, 2722 KB

Open AccessReview

Targeting Cancer-Associated Fibroblasts in Prostate Cancer: Recent Advances and Therapeutic Opportunities

by Peng Chen, Junhao Chen, Peiqin Zhan, Xinni Ye, Li Zhao, Zhongsong Zhang, Jieming Zuo, Hongjin Shi, Xiangyun Li, Songhong Wu, Yuanzhi Fu, Haifeng Wang and Shi Fu

Cancers 2026, 18(1), 151; https://doi.org/10.3390/cancers18010151 - 31 Dec 2025

Advanced prostate cancer, particularly castration-resistant disease, remains challenging to treat due to intratumoral heterogeneity, immune exclusion, and a suppressive tumor microenvironment. Within this ecosystem, cancer-associated fibroblasts shape tumor–stroma communication, but their marked heterogeneity and plasticity complicate classification and make indiscriminate fibroblast depletion potentially [...] Read more.

Advanced prostate cancer, particularly castration-resistant disease, remains challenging to treat due to intratumoral heterogeneity, immune exclusion, and a suppressive tumor microenvironment. Within this ecosystem, cancer-associated fibroblasts shape tumor–stroma communication, but their marked heterogeneity and plasticity complicate classification and make indiscriminate fibroblast depletion potentially ineffective or even harmful. This review summarizes recent progress in fibroblast origins, functional subtypes, and fibroblast-driven mechanisms that promote tumor progression and therapy resistance, as well as emerging therapeutic opportunities in prostate cancer. We conducted a structured literature search of PubMed, ScienceDirect, and major publisher platforms (including Nature and SpringerLink) from database inception to 15 February 2025, supplemented by targeted manual screening of reference lists. Evidence from single-cell/spatial-omics and mechanistic studies indicates that prostate tumors contain multiple fibroblast programs that occupy distinct niches yet can interconvert. Across these studies, it was found that these fibroblasts contribute to immune suppression, extracellular matrix remodeling and stromal barrier formation, angiogenesis, and metabolic support, collectively limiting drug penetration and reinforcing immune evasion; therapeutic pressure can further rewire fibroblast states and resistance-associated signaling. Overall, the literature supports a shift toward function- and subtype-directed intervention rather than “one-size-fits-all” targeting, with promising directions including precision targeting and reversible reprogramming, rational combination strategies, and localized delivery approaches that reduce stromal barriers while preserving tissue homeostasis in high-risk and treatment-refractory prostate cancer. Full article

(This article belongs to the Special Issue Mechanistic Insights and Therapeutic Advances in the Prostate Tumor Microenvironment)

14 pages, 451 KB

Open AccessArticle

The Cost-Effectiveness of Organized National Colorectal Cancer Screening Program in Croatia

by August Cesarec, Nataša Antoljak, Ivana Brkić Biloš, Mario Šekerija, Maja Vajagić and Neven Ljubičić

Cancers 2026, 18(1), 150; https://doi.org/10.3390/cancers18010150 - 31 Dec 2025

Background/Objectives: Colorectal cancer is the most frequently diagnosed cancer and second by mortality among all cancers in Croatia. The Organized National Colorectal Cancer Screening Program was introduced by the government in 2007. It targets individuals aged 50–74 years with a biennial screening with [...] Read more.

Background/Objectives: Colorectal cancer is the most frequently diagnosed cancer and second by mortality among all cancers in Croatia. The Organized National Colorectal Cancer Screening Program was introduced by the government in 2007. It targets individuals aged 50–74 years with a biennial screening with a guaiac fecal occult blood test (gFOBT). The aim of this study is to analyze the costs associated with colorectal cancer in Croatia and to compare the cost-effectiveness of three screening strategies: no screening, biennial gFOBT, and biennial fecal immunochemical testing (FIT). Patients and methods: A model was developed to compare the three screening scenarios. The model simulated a cohort of 10,000 patients aged 50 years without colorectal cancer. Health outcomes and associated costs were projected over a five-year time horizon. The model outcomes include the number of newly diagnosed colorectal cancer cases, number of colorectal cancer-related deaths, life-years gained, and costs per life-year gained. Results: The average five-year costs per patient for the treatment of advanced cancer are EUR 39,802, which is substantially higher than the average costs of EUR 16,897 per patient across all stages. The implemented model indicates that both screening options yielded improved health outcomes at lower costs compared with no screening. FIT is considered the preferred screening option due to its higher sensitivity, greater health outcomes, and lower costs relative to gFOBT. Conclusions: The introduction of FIT screening instead of gFOBT could increase screening uptake for colorectal cancer, improve health outcomes, and reduce healthcare expenditures and the economic burden associated with colorectal cancer in Croatia. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

20 pages, 2857 KB

Open AccessReview

Fluorescence-Guided Surgery in Pediatric Oncology: Current Practice and Future Directions

by Dominique C. Simons, Lorenz H. M. van Schalkwijk, Michiel A. J. van de Sande, Alexander L. Vahrmeijer, Marc H. W. A. Wijnen, Alida F. W. van der Steeg and Willemieke S. F. J. Tummers

Cancers 2026, 18(1), 149; https://doi.org/10.3390/cancers18010149 - 31 Dec 2025

Background/Objectives: Achieving complete, yet safe tumor resections are particularly challenging in pediatric oncology due to infiltrative tumor growth patterns, small patient size, and the close proximity to critical structures. Fluorescence-guided surgery (FGS) enhances visualization of anatomy, tissue perfusion, and tumor tissue in [...] Read more.

Background/Objectives: Achieving complete, yet safe tumor resections are particularly challenging in pediatric oncology due to infiltrative tumor growth patterns, small patient size, and the close proximity to critical structures. Fluorescence-guided surgery (FGS) enhances visualization of anatomy, tissue perfusion, and tumor tissue in real time, potentially improving surgical precision. While widely explored in adults, its application in pediatric oncology remains limited. This review summarizes current evidence on FGS in pediatric oncology, with emphasis on the unique challenges inherent to this field. Finally, strategies to accelerate clinical translation and assess the potential clinical value are proposed. Methods: A narrative review of the literature was conducted using PubMed and Embase to identify English-language publications on FGS in pediatric oncology up to September 2025. Search terms included Fluorescence, Pediatrics, Neoplasms, and Surgery. Results: Studies commonly reported that indocyanine green (ICG) aids in lymph node mapping, hepatoblastoma resection, and visualization of vascular structures and tissue perfusion. However, its non-specific nature and lack of histopathological validation limits diagnostic precision in tumor imaging. Tissue-specific agents are being investigated in first-in-humans trials to improve sensitivity and specificity, and to identify ureters and nerves. Conclusions: In this review, the challenging roadmap for advancing FGS in pediatric oncology is presented. Closing current gaps will require coordinated efforts in target discovery, agent design, and clinical validation. If successful, FGS can evolve from a promising tool into an indispensable clinical technique that enhances surgical precision, reduces recurrence, and ultimately improves long-term outcomes for children with cancer. Full article

(This article belongs to the Special Issue Research on Fluorescence-Guided Surgery in Cancer Treatment)

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20 pages, 446 KB

Open AccessReview

Endometrial Hyperplasia: Current Insights into Epidemiology, Risk Factors, and Clinical Management

by Apostolia Galani, Sofoklis Stavros, Efthalia Moustakli, Anastasios Potiris, Athanasios Zikopoulos, Ismini Anagnostaki, Konstantinos Zacharis, Maria Paraskevaidi, Deirdre Lyons, Stefania Maneta-Stavrakaki, Nikolaos Thomakos, Maria Kyrgiou and Ekaterini Domali

Cancers 2026, 18(1), 148; https://doi.org/10.3390/cancers18010148 - 31 Dec 2025

Endometrial hyperplasia (EH) comprises a spectrum of abnormal proliferative changes in the endometrium, ranging from benign glandular overgrowth to lesions with substantial malignant potential. The importance of risk stratification and early identification is highlighted by the growing recognition of EH as a precursor [...] Read more.

Endometrial hyperplasia (EH) comprises a spectrum of abnormal proliferative changes in the endometrium, ranging from benign glandular overgrowth to lesions with substantial malignant potential. The importance of risk stratification and early identification is highlighted by the growing recognition of EH as a precursor to endometrial cancer. The main causes of EH, according to epidemiological research, include obesity, polycystic ovarian syndrome (PCOS), metabolic dysfunction, and extended exposure to unopposed estrogen. Emerging molecular markers, histological analysis, and imaging are all necessary for a proper diagnosis of EH because it might appear with vague clinical symptoms such as irregular uterine bleeding. Surgical intervention or progestin therapy are two possible management techniques for EH, depending on the lesion’s intricacy and the patient’s medical history, including fertility issues. Personalized therapy techniques and recent developments in molecular profiling have the potential to enhance patient outcomes by matching treatment to tumor biology and individual risk profiles. This review highlights the translational potential of molecular insights while synthesizing the most recent data on the epidemiology, risk factors, diagnostic techniques, and therapy of EH. A deeper comprehension of these elements is necessary to maximize treatment results and stop the development of endometrial cancer. Full article

(This article belongs to the Special Issue Cancer Screening and Primary Care)

14 pages, 691 KB

Open AccessArticle

Visual Impairment and Cancer Risk: A Nationwide Cohort Study of Adult Swedish Men and Women

by Leda Pistiolis, Henrik Litsne, Roger Olofsson Bagge and Kristian F. Axelsson

Cancers 2026, 18(1), 147; https://doi.org/10.3390/cancers18010147 - 31 Dec 2025

Background: Visual impairment is linked to a broad spectrum of health conditions. Nevertheless, there is an absence of large cohort studies investigating cancer risk in the visually impaired compared to seeing controls. The aim of this study was to investigate whether visually impaired [...] Read more.

Background: Visual impairment is linked to a broad spectrum of health conditions. Nevertheless, there is an absence of large cohort studies investigating cancer risk in the visually impaired compared to seeing controls. The aim of this study was to investigate whether visually impaired adults have an increased risk for various types of cancer, compared to seeing controls. Methods: This was a retrospective cohort study comparing visually impaired adults aged 40 and over and 1:5 matched controls (by sex, birth year, and county of residence), between 2002 and 2018. Data were extracted from the Swedish National patient Registry, Statistics Sweden and from the Swedish Cause of Death Registry. A total of 48,493 adult Swedish men (44%) and women (56%), with a median age of 77 years (IQR: 64–86), with various degrees of visual impairment, from mild to total blindness, and 242,465 matched controls were followed up for a median of 5.1 (IQR 2.9–8.6) and 6.0 (IQR 3.6–9.8) years, respectively. The main outcomes included overall cancer incidence and incidence of different types of cancer. Results: Data analysis showed that visually impaired adults had an 18% significantly increased risk of any cancer (HR 1.18, 95% CI 1.16–1.20) when compared to seeing controls. The risk was also significantly increased for most cancers, with HRs ranging from 2.59 (95% CI 2.21–3.03) for brain cancer to 1.19 (95% CI 1.11–1.27) for breast cancer. No interaction was observed between cancer of any type and sex (p = 0.47). An elevated risk for all cancers in the visually impaired was observed across all age-groups: HR of 1.37 (95% CI 1.30–1.43) for ages 40–64, HR 1.17 (95% CI 1.13–1.20) for ages 65–79, and HR 1.11 (95% CI 1.08–1.15) for ages over 80. The risk of death was 60% higher among the cases compared to controls (HR 1.60, 95% CI 1.58–1.63). Conclusions: In this retrospective study of older adults, visual impairment was associated with increased cancer risk both overall and for specific types of cancer, in both sexes and across different age divisions of the cohort. These findings indicate the need for adjustments in health care polices in order to ensure equity in medical services. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

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16 pages, 2251 KB

Open AccessArticle

Spontaneous cSCC Murine Model Shows Limited Response to PD-1 Blockade and Radiation Combination Therapy

by Tara M. Hosseini, Laura Ho, Tammy B. Pham, Alfredo Molinolo, Riley Jones, David Vera, Andrew Sharabi, Soo J. Park and Theresa Guo

Cancers 2026, 18(1), 146; https://doi.org/10.3390/cancers18010146 - 31 Dec 2025

Background/Objectives: Non-melanoma skin cancer, which includes cutaneous squamous cell carcinoma (cSCC), ranks as the 5th most common cancer globally with high morbidity and more total deaths than melanoma despite having a lower mortality rate. While most cSCC cases can be treated with [...] Read more.

Background/Objectives: Non-melanoma skin cancer, which includes cutaneous squamous cell carcinoma (cSCC), ranks as the 5th most common cancer globally with high morbidity and more total deaths than melanoma despite having a lower mortality rate. While most cSCC cases can be treated with surgery, locally advanced, metastatic, and high-risk cSCC tumors are associated with a worse prognosis with higher rates of recurrence and require multimodality therapy. However, there is limited data on animal models of cutaneous squamous cell carcinoma for the use of combinatory immunotherapy and radiation. Methods: In this study, spontaneously generated tumors using DMBA/TPA were treated over three weeks with either IgG control, anti-PD1 antibody monotherapy, 8 Gy of localized radiation, or a combination of anti-PD1 and 8 Gy of radiation followed by anti-PD1 therapy. Results: We found that while anti-PD1 therapy showed a trend toward slowed tumor growth compared to controls, this difference was not statistically significant (p = 0.0775), with most mice showing continued tumor progression. Preliminary histological analysis suggested that anti-PD1 treatment increased CD8+ T cell infiltration, and the addition of radiation further enhanced CD8+ responses but added greater variability. A pathologic review revealed that irradiated tumors were associated with fibroblastic spindle-like cell morphology. Conclusions: This animal model represents a potential preclinical model for studying CSCC with limited responses to immunotherapy to understand potential mechanisms of resistance. Full article

(This article belongs to the Special Issue Recent Advances in Skin Cancers)

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19 pages, 319 KB

Open AccessReview

Oral Microbiome in Oral Cancer Research from Sampling to Analysis: Strategies, Challenges, and Recommendations

by Kelly Yi Ping Liu, Andrew Huang, Catherine Pepin, Ya Shen, Phoebe Tsang and Catherine F. Poh

Cancers 2026, 18(1), 145; https://doi.org/10.3390/cancers18010145 - 31 Dec 2025

The oral microbiome has become an emerging focus of oral cancer research, with growing evidence linking microbial communities to disease development, progression, and prognosis. However, there is limited consensus on optimal sampling strategies, storage methods, and analytical approaches. This narrative review critically evaluates [...] Read more.

The oral microbiome has become an emerging focus of oral cancer research, with growing evidence linking microbial communities to disease development, progression, and prognosis. However, there is limited consensus on optimal sampling strategies, storage methods, and analytical approaches. This narrative review critically evaluates current strategies for sampling, preservation, DNA extraction, sequencing, and data analysis in oral microbiome research related to oral cancer. We compared commonly used sampling methods, including saliva, oral rinse, swab, brush, and tissue biopsy, and reviewed preservation conditions, extraction kits, sequencing platforms, and analytical pipelines reported in recent oral microbiome studies. Sampling approaches affect microbial yield and site specificity. Saliva and oral rinse samples are convenient and noninvasive but may dilute lesion-specific microbial signals, whereas lesion-directed swabbing or brushing yields greater microbial biomass and biological relevance. Preservation media and storage temperature significantly influence microbial stability, and DNA extraction methods vary in their ability to remove host DNA. Although 16S rRNA gene sequencing remains the most common approach, shotgun metagenomics offers higher resolution and function insights but is still limited by clinical applicability. Differences in data pre- and post-processing models and normalization strategies further contribute to inconsistent microbial profiles. Given that oral mucosal sites differ markedly in structure and microenvironment, careful consideration is required to ensure that collected samples accurately represent the biological question being addressed. Methodological consistency across all workflow stages—from collection to analysis—is essential to generate reproducible, high-quality data and to enable reliable translation of oral microbiome research into clinical applications for cancer detection and risk assessment. Together, these insights provide a framework to guide future study design and support the development of clinically applicable microbiome-based biomarkers. Full article

(This article belongs to the Section Clinical Research of Cancer)

15 pages, 462 KB

Open AccessReview

Advances in Neoantigen-Based Cancer Vaccines

by An-Chih Wu, Yusuke Nakamura and Kazuma Kiyotani

Cancers 2026, 18(1), 144; https://doi.org/10.3390/cancers18010144 - 31 Dec 2025

Neoantigen-based immunotherapies harness somatic mutations as tumor-specific targets and represent a major advance in personalized cancer treatment. Since neoantigens are presented exclusively on cancer cells, they enable highly selective T-cell recognition with minimal off-tumor toxicity. Neoantigen vaccines are rapidly emerging as a versatile [...] Read more.

Neoantigen-based immunotherapies harness somatic mutations as tumor-specific targets and represent a major advance in personalized cancer treatment. Since neoantigens are presented exclusively on cancer cells, they enable highly selective T-cell recognition with minimal off-tumor toxicity. Neoantigen vaccines are rapidly emerging as a versatile class of personalized cancer immunotherapies designed to prime tumor-specific T cells by targeting somatic mutations unique to each patient’s tumor. Multiple types of neoantigen vaccines, using peptide, mRNA, and DNA, have shown feasibility, safety, and immunogenicity across diverse solid tumors. Emerging comparative data indicate that the vaccines using peptide-pulsed dendritic cells (DCs) elicit higher per-epitope CD8⁺ T cell responses than mRNA-based vaccines, likely due to more efficient class I presentation of synthetic peptides and ex vivo-loaded DCs. In contrast, mRNAs, despite their capacity of targeting multiple neoantigen peptides simultaneously, often induce CD4⁺-dominant responses due to immunodominance patterns during antigen processing. Recent clinical trials in melanoma, glioblastoma, pancreatic cancer, and other types of cancer have demonstrated not only robust immune activation but also encouraging relapse-free outcomes when administered in adjuvant settings. Treatment timing strongly influenced immune responsiveness; patients with early-stage disease or those vaccinated after surgical resection generally exhibit more preserved systemic immunity and greater vaccine-induced T cell expansion compared to those with advanced disease. Future progress will rely on improved neoantigen prediction, including incorporation of post-translationally modified antigenic targets and acceleration of manufacturing pipelines to ensure timely, personalized vaccine delivery. Collectively, neoantigen vaccines offer substantial promise for integration into next-generation cancer treatment strategies. Full article

(This article belongs to the Special Issue Neoantigen Vaccines for Cancer Therapy)

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28 pages, 2054 KB

Open AccessReview

Non-Coding RNA-GATA Axis: Mechanisms and Implications in Cancer Progression and Metastases

by Aviral Kumar, Uzini Devi Daimary, Mangala Hegde, Mohamed Abbas, Mohammed S. Alqahtani, Hassan Ali Almubarak, Vinay Tergaonkar, Gautam Sethi and Ajaikumar B. Kunnumakkara

Cancers 2026, 18(1), 143; https://doi.org/10.3390/cancers18010143 - 31 Dec 2025

GATA transcription factors, defined by their zinc finger DNA-binding domains, are central regulators of tissue development. They modulate gene expression by activating or repressing transcription, thereby coordinating cellular differentiation and cell cycle exit to maintain homeostasis. In progenitor cells, GATA factors promote proliferation, [...] Read more.

GATA transcription factors, defined by their zinc finger DNA-binding domains, are central regulators of tissue development. They modulate gene expression by activating or repressing transcription, thereby coordinating cellular differentiation and cell cycle exit to maintain homeostasis. In progenitor cells, GATA factors promote proliferation, whereas in differentiating cells, they drive maturation and induce cell cycle arrest. Dysregulation of GATA factors has been linked to tumorigenesis and contributes significantly to cancer progression and metastasis. Mutations in GATA factor genes correlate with poor prognosis in multiple cancers, where they influence key oncogenic processes, including sustained proliferative signaling, activation of epithelial–mesenchymal transition, angiogenesis, resistance to cell death, and immune escape. Importantly, their context-dependent roles across tumor types highlight the complexity of their functions in malignancies. Meanwhile, non-coding RNAs have emerged as critical regulators of gene expression, acting as either tumor suppressors or oncogenes by modulating chromatin dynamics, transcription factor activity, and mRNA stability. Despite this, the regulation of GATA transcriptional activity by non-coding RNAs remains largely unexplored. This review highlights the role of GATA factors in regulating EMT and metastasis and focuses on the interplay between non-coding RNAs and GATA transcription factors in cancer progression, proposing a novel regulatory axis with potential implications for biomarker discovery and therapeutic targeting. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cancer Progression and Metastasis)

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16 pages, 2041 KB

Open AccessReview

A Review of ARID1A’s Role in Breast Cancer Progression: Context-Dependent Mechanisms and Therapeutic Implications

by Gopalakrishnan Shankari, Dhamodharan Prabhu, Muthusamy Sureshan, Jeyaraman Jeyakanthan and Sundararaj Rajamanikandan

Cancers 2026, 18(1), 142; https://doi.org/10.3390/cancers18010142 - 31 Dec 2025

ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, plays a context-dependent function in cancer, acting both as a tumor suppressor and, in certain conditions, as an oncogene. ARID1A, as a tumor suppressor, maintains transcriptional regulation, genomic stability, and cellular differentiation. In [...] Read more.

ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, plays a context-dependent function in cancer, acting both as a tumor suppressor and, in certain conditions, as an oncogene. ARID1A, as a tumor suppressor, maintains transcriptional regulation, genomic stability, and cellular differentiation. In breast cancer, ARID1A loss-of-function leads to dysregulation of cell cycle checkpoints and impaired DNA repair and promotes epithelial-to-mesenchymal transition (EMT), jointly accelerating tumor proliferation and increasing therapeutic resistance. Notably, context-dependent ARID1A loss-of-function often concurs with activation of the PI3K/AKT signaling pathway and corresponds with poor prognosis. On the contrary, aberrant ARID1A overexpression can provoke oxidative stress and agitate the cytochrome P450 system, potentially facilitating early tumorigenesis. Consequently, understanding ARID1A’s dual and context-dependent role highlights its potential as a biomarker and therapeutic target in precision oncology. Full article

(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)

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17 pages, 491 KB

Open AccessReview

Chemotherapy for Gastric Cancer Is Not Solely the Domain of the Oncologist

by Gabriel Samasca, Ioana Badiu Tisa, Calin Lazar, Ciprian N. Silaghi, Diana Deleanu, Adriana Muntean and Iulia Lupan

Cancers 2026, 18(1), 141; https://doi.org/10.3390/cancers18010141 - 31 Dec 2025

Adverse effects of chemotherapeutic agents remain a significant clinical challenge in the management of gastric cancer. Across the literature, discussions of chemotherapy consistently document a range of toxicities, underscoring that even when treatment halts disease progression, it can leave substantial clinical sequelae. Chemotherapy [...] Read more.

Adverse effects of chemotherapeutic agents remain a significant clinical challenge in the management of gastric cancer. Across the literature, discussions of chemotherapy consistently document a range of toxicities, underscoring that even when treatment halts disease progression, it can leave substantial clinical sequelae. Chemotherapy can impact virtually every organ system, producing multiorgan toxicity with meaningful implications for patient quality of life and treatment feasibility. When initiating a new chemotherapy regimen, prior lack of therapeutic benefit is often associated with difficult recovery or inability to tolerate subsequent chemotherapy, thereby constraining future therapeutic options. Given these considerations and the current absence of universally personalized treatment, a multidisciplinary team—comprising a medical oncologist, gastroenterologist, and internist—is essential to the planning and execution of chemotherapy regimens. We recommend that these chemotherapy regimens be administered within internal medicine departments, in collaboration with the medical oncologist and gastroenterologist, because in many cases the adverse effects outweigh the potential benefits of chemotherapy. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy: 2nd Edition)

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4 pages, 166 KB

Open AccessEditorial

Liquid Biopsy in Cancer: The Importance of Integrating Bioinformatics Approaches Towards the Development of a Personalized Molecular Profile

by Areti Strati, Kostas A. Papavassiliou and Athanasios G. Papavassiliou

Cancers 2026, 18(1), 140; https://doi.org/10.3390/cancers18010140 - 31 Dec 2025

Liquid biopsy is now a valuable complementary tool that oncologists use to obtain a more complete picture of their patients’ condition in real time [...] Full article

(This article belongs to the Special Issue Circulating Tumor Cells (CTCs) and the Implementation of Liquid Biopsy (2nd Edition))

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