Cancers

17 pages, 642 KB

Open AccessReview

FGFR Testing in Metastatic Urothelial Carcinoma—Who, When, and How to Test

by André Mansinho, José Carlos Machado, Cátia Faustino, Arnaldo Figueiredo, João Moreira Pinto, Nuno Vau, João Ramalho-Carvalho and Manuel R. Teixeira

Cancers 2026, 18(3), 444; https://doi.org/10.3390/cancers18030444 - 29 Jan 2026

Abstract

Metastatic urothelial carcinoma (mUC) is a lethal cancer with limited therapeutic options. Advances in genomic and transcriptomic research have deepened the understanding of mUC biology, leading to the identification of clinically relevant molecular alterations that represent potential actionable targets. This has broadened the [...] Read more.

Metastatic urothelial carcinoma (mUC) is a lethal cancer with limited therapeutic options. Advances in genomic and transcriptomic research have deepened the understanding of mUC biology, leading to the identification of clinically relevant molecular alterations that represent potential actionable targets. This has broadened the treatment landscape of the disease to include novel agents, such as antibody–drug conjugates (e.g., enfortumab vedotin) and targeted therapies, including the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib. Genomic alterations in FGFR3 are well-established oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR-targeted therapies. The phase III THOR trial demonstrated the clinical benefit of erdafitinib in previously treated mUC patients harboring FGFR3 alterations and supported its subsequent approval by the European Medicines Agency. In this context, accurate molecular profiling is essential to guide patient selection for FGFR inhibitor therapy. Equally important is the standardization and timely implementation of FGFR3 testing in clinical practice to optimize treatment planning. This review addresses key considerations in FGFR3 testing in mUC and discusses how it can be routinely incorporated into clinical practice. Full article

(This article belongs to the Section Cancer Biomarkers)

14 pages, 1104 KB

Open AccessArticle

MAGE (Multimodal AI-Enhanced Gastrectomy Evaluation): Comparative Analysis of Machine Learning Models for Postoperative Complications in Central European Gastric Cancer Population

by Wojciech Górski, Marcin Kubiak, Amir Nour Mohammadi, Maksymilian Podleśny, Gian Luca Baiocchi, Manuele Gaioni, Santo Vincent Grasso, Andrew Gumbs, Timothy M. Pawlik, Bartłomiej Drop, Albert Chomątowski, Zuzanna Pelc, Katarzyna Sędłak, Michał Woś and Karol Rawicz-Pruszyński

Cancers 2026, 18(3), 443; https://doi.org/10.3390/cancers18030443 (registering DOI) - 29 Jan 2026

Abstract

Introduction: By leveraging dedicated datasets and predictive modeling, machine-learning (ML) algorithms can estimate the probability of both short- and long-term outcomes after surgery. The aim of this study was to evaluate the ability of ML-based models to predict postoperative complications in patients [...] Read more.

Introduction: By leveraging dedicated datasets and predictive modeling, machine-learning (ML) algorithms can estimate the probability of both short- and long-term outcomes after surgery. The aim of this study was to evaluate the ability of ML-based models to predict postoperative complications in patients with gastric cancer (GC) undergoing multimodal therapy. In particular, we aimed to develop a free, publicly accessible online calculator based on preoperative variables. Materials and Methods: Patients with histologically confirmed locally advanced (cT2-4N0-3M0) GC who underwent multimodal treatment with curative intent between 2013 and 2023 were included in the study. ML models evaluation pipeline was used with Stratified 5-Fold Cross-Validation. Results: A total of 368 patients were included in the final analytic cohort. Among five algorithm classes under 5-fold cross-validation, Compute Area Under the Receiver Operating Characteristic Curve (ROC AUC) was 0.9719, 0.9652, 0.9796, 0.8339 and 0.7581 for XGBoost, Catboost, Random Forest, SVM and Logistic Regression, respectively. Macro F1 was 0.8714, 0.5094, 0.8820, 0.8714 and 0.4579 for XGBoost, SVM, Random Forest, CatBoost and Logistic Regression, respectively. Overall Accuracy was 0.8897, 0.5980, 0.8885, 0.8750 and 0.5466 for XGBoost, SVM, Random Forest, CatBoost and Logistic Regression models, respectively. Conclusions: In this Central and Eastern European cohort of patients with locally advanced GC, ML models using non-linear decision rules-particularly Random Forest and XGBoost- substantially outperformed conventional linear approaches in predicting the severity of postoperative complications. Prospective external validation is needed to clarify the model’s clinical utility and its potential role in perioperative decision support. Full article

(This article belongs to the Special Issue Contemporary Advances and Challenges in Multimodal Management of Gastric Cancer)

16 pages, 1389 KB

Open AccessArticle

Development of a Computer Program for Determining the Dose of Laser Radiation (860 nm) Received by Tumor and Breast Tissue

by Vladimir Alexander Mikhaylov, Nadezhda Voltchenko, Dmitry Mikhailov, Vladimir Gladyshev and Evgene Sharandin

Cancers 2026, 18(3), 442; https://doi.org/10.3390/cancers18030442 - 29 Jan 2026

Abstract

Laser therapy (860–910 nm) has been used to treat cancer since 1988. A key challenge is determining the dose of laser radiation absorbed by the tumor. Attenuation coefficients of laser radiation were determined for different breast tissues at various tissue thicknesses and beam [...] Read more.

Laser therapy (860–910 nm) has been used to treat cancer since 1988. A key challenge is determining the dose of laser radiation absorbed by the tumor. Attenuation coefficients of laser radiation were determined for different breast tissues at various tissue thicknesses and beam angles. These results enable the development of a methodology for determining optimal irradiation modes by considering both the absorbed dose of laser radiation and objective examination data (ultrasound, mammography, CT, and MRI). Full article

(This article belongs to the Topic Innovations in Physics and Radiobiology Studies of Particle Therapy)

18 pages, 21901 KB

Open AccessArticle

Lentiviral Dendritic Cell Vaccine Targeting Claudin-18.2 Elicits Potent Antitumor Immunity Against Gastric Cancer

by Bowen Zheng, Wenqing Zhang, Dan Zhou, Miao Fu, Fanzhuoran Lou, Xintian Huang, Xiaowen Xie, Yunli Gong, Kaiyi Rong, Yongxiang Hong, Yanyan Zhan, Li Xiao and Tianhui Hu

Cancers 2026, 18(3), 441; https://doi.org/10.3390/cancers18030441 - 29 Jan 2026

Abstract

Background: Claudin-18.2 (CLDN18.2) has emerged as a promising therapeutic target for gastric cancer due to its frequent and specific expression in malignant lesions. Dendritic cell (DC)-based vaccines represent a potent strategy for inducing antitumor immunity; however, their efficacy against solid tumors, such as [...] Read more.

Background: Claudin-18.2 (CLDN18.2) has emerged as a promising therapeutic target for gastric cancer due to its frequent and specific expression in malignant lesions. Dendritic cell (DC)-based vaccines represent a potent strategy for inducing antitumor immunity; however, their efficacy against solid tumors, such as gastric cancer, remains challenging. Methods: We developed a lentiviral vector encoding human CLDN18.2 (Lv-CLDN18.2) to generate antigen-loaded DC vaccines. In vitro, human monocyte-derived DCs were transduced and co-cultured with autologous T cells to induce cytotoxic T lymphocytes (CTLs). CTL function was assessed by flow cytometry, cytokine ELISA, and cytotoxicity assays against CLDN18.2-positive gastric cancer cells. In vivo, the therapeutic efficacy of the DC vaccine was evaluated in a syngeneic mouse model subcutaneously inoculated with MFC-CLDN18.2 cells. Results: We successfully produced high-titer Lv-CLDN18.2 and established stable CLDN18.2-positive gastric cancer cell lines. Lv-CLDN18.2-transduced DCs exhibited a mature phenotype with upregulated co-stimulatory (CD80/CD86) and antigen-presenting molecules (HLA-ABC/DR). These DCs potently stimulated CTLs, leading to a significantly higher proportion of activated CD8⁺CD25⁺ T cells, enhanced secretion of IFN-γ and TNF-α, and potent, specific lysis of CLDN18.2-positive target cells in vitro. In mouse models, vaccination with Lv-CLDN18.2-DCs significantly suppressed tumor growth, which was associated with robust CD8⁺ T cell infiltration, reduced tumor cell proliferation (Ki-67), and decreased CLDN18.2-positive tumor cells in vivo. Conclusions: Our study demonstrates that a CLDN18.2-targeting DC vaccine can effectively induce potent antigen-specific CTL responses and elicit significant antitumor immunity in a preclinical model. These findings provide a strong rationale for the clinical development of CLDN18.2-directed DC-based immunotherapy for gastric cancer. Full article

(This article belongs to the Section Molecular Cancer Biology)

12 pages, 349 KB

Open AccessArticle

Endometrial Mixed and Mixed-Feature Carcinomas: Small Cohort Clinicopathologic and Molecular Studies

by Swati Bhardwaj, Mona Saleh, Yayoi Kinoshita, Rachel Brody, Olga Lukatskaya, Stephanie V. Blank, Brett Baskovich and Tamara Kalir

Cancers 2026, 18(3), 440; https://doi.org/10.3390/cancers18030440 - 29 Jan 2026

Abstract

Objectives: To examine the clinical, pathologic, and molecular features of mixed and mixed feature endometrial carcinomas and compare them to pure serous carcinoma and pure endometrioid carcinoma. Methods: The study analyzed the clinical characteristics, histologic composition, and molecular genetic profiles of mixed and [...] Read more.

Objectives: To examine the clinical, pathologic, and molecular features of mixed and mixed feature endometrial carcinomas and compare them to pure serous carcinoma and pure endometrioid carcinoma. Methods: The study analyzed the clinical characteristics, histologic composition, and molecular genetic profiles of mixed and mixed feature endometrial cancers, with a focus on shared and distinct mutations. Patient demographics, disease-free survival, and molecular alterations, including in TP53, PIK3CA, TERT, MAP2K1 genes, and ERBB2 gene amplifications, were assessed and compared to pure serous and pure endometrioid carcinomas. Results: Patients with mixed and mixed-feature carcinomas were older (median age: 73 years) and had worse disease-free survival (median: 23 months) than those with pure endometrioid carcinoma (median: 48 months). Mixed and mixed-feature carcinomas were histologically high-grade, most commonly comprising serous and endometrioid components. Molecular profiling supported a clonal origin of these tumors, with identical TP53 and PIK3CA gene mutations between the two histologic components in each case. There were additional gene mutations (e.g., TERT and MAP2K1) found in higher-grade components. ERBB2 amplifications were more frequent in the mixed carcinomas groups (33%) compared to pure serous (11%) and pure endometrioid carcinomas (0%). Some of the mixed and mixed-feature carcinomas also showed FBXW7 mutations, not seen in either the pure endometrioid or pure serous carcinomas. Conclusions: Mixed and mixed-feature carcinomas share origins with pure endometrial serous and endometrioid carcinoma subtypes but exhibit distinct molecular alterations. These findings highlight the importance of molecular subtyping for diagnosis and treatment planning. Future research could focus on larger cohorts and targeted sequencing to better understand the pathogenesis of mixed and mixed-feature carcinomas in order to refine therapeutic strategies. Full article

(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)

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14 pages, 821 KB

Open AccessArticle

Cost-Effectiveness of a Quality of Life Predictor to Guide Psychosocial Support in Breast Cancer

by Tuukka Hakkarainen, Ira Haavisto, Mikko Nuutinen, Yrjänä Hynninen, Paula Poikonen-Saksela, Johanna Mattson, Haridimos Kondylak, Eleni Kolokotroni, Ketti Mazzocco, Berta Sousa, Isabel Manica, Ruth Pat-Horenczyk and Riikka-Leena Leskelä

Cancers 2026, 18(3), 439; https://doi.org/10.3390/cancers18030439 - 29 Jan 2026

Abstract

Introduction: Women with breast cancer experience psychological distress, and resilience-strengthening psychosocial support may improve their quality of life (QoL). Identifying those at risk of low QoL is challenging. This study evaluated the cost-effectiveness of a machine learning-based QoL predictor to support clinical [...] Read more.

Introduction: Women with breast cancer experience psychological distress, and resilience-strengthening psychosocial support may improve their quality of life (QoL). Identifying those at risk of low QoL is challenging. This study evaluated the cost-effectiveness of a machine learning-based QoL predictor to support clinical decision-making regarding psychosocial support (sample size: 660). Methods: A decision tree cost–utility model was developed to compare four decision-making strategies in offering psychosocial support: the clinician alone, the QoL predictor alone, the clinician supported by the predictor, and no prediction with no psychosocial support. QoL after one year was used as a proxy for resilience. Costs, health outcomes, and net monetary benefits (NMBs) were estimated using a one-year time horizon. Incremental cost-effectiveness ratios (ICERs) were calculated and dominance assessed. A societal scenario analysis incorporated productivity losses. A probabilistic sensitivity analysis generated cost-effectiveness acceptability curves. Results: Clinicians supported by the QoL predictor produced the highest NMB (EUR 16,349) and the greatest quality-adjusted life year (QALY) gain (0.759), with an ICER of EUR 22,892 compared with the next least costly strategy. Clinician-only prediction and predictor-only approaches were dominated or extendedly dominated. Under the societal perspective, all strategies produced negative NMB values due to productivity losses, but the overall ranking remained unchanged. The probabilistic sensitivity analysis showed that the combined clinician and predictor strategy had a 69% probability of being cost-effective at a willingness to pay threshold of EUR 30,000. Conclusions: Combining clinician judgement with the machine learning-based QoL predictor improved the targeting of psychosocial support and was the most cost-effective strategy. Further prospective and comparative studies are needed to confirm its long-term effectiveness and cost-effectiveness in clinical practice. Full article

(This article belongs to the Special Issue Cost-Effectiveness Studies in Cancers)

29 pages, 2090 KB

Open AccessArticle

Liquid Biopsy Analysis of the EV-Associated Micro-RNA Signature in Vulvar Carcinoma May Benefit Disease Diagnosis and Prognosis

by Friederike Borchardt, Leonie Kleinholz, Anna Jaeger, Jana Löptien, Vanessa Vohl, Jolanthe Kropidlowski, Klaus Pantel, Eik Vettorazzi, Linn Woelber, Harriet Wikman and Katharina Effenberger

Cancers 2026, 18(3), 438; https://doi.org/10.3390/cancers18030438 - 29 Jan 2026

Abstract

Background: Vulvar cancer mainly affects postmenopausal women, but its incidence is rising among younger individuals due to persistent HPV infection. Validated diagnostic biomarkers remain lacking, though circulating exosomal microRNAs (exomiRs) have recently emerged as promising liquid biopsy tools across various cancers. Objective: The [...] Read more.

Background: Vulvar cancer mainly affects postmenopausal women, but its incidence is rising among younger individuals due to persistent HPV infection. Validated diagnostic biomarkers remain lacking, though circulating exosomal microRNAs (exomiRs) have recently emerged as promising liquid biopsy tools across various cancers. Objective: The purpose of this study was to identify a panel of dysregulated plasma-derived extracellular vesicle (EV)-associated miRNAs, hereafter referred to as exosomal micro-RNAs, as liquid biopsy markers for the detection of vulvar cancer and for assessment of HPV-positivity. Methods: Five healthy donor (HD) and 10 vulvar cancer samples underwent Next-Generation Sequencing to screen for differentially expressed exomiRs. The seven most dysregulated and four stably expressed exomiRs were subsequently analyzed in 81 cancer and 60 HD samples by qRT-PCR. Differential expression was determined by the 2^−ΔΔCT method. Binary regression was used to construct an exomiR panel. HPV status was assessed using mass spectrometry. Results: Five single exomiRs showed a statistically significant dysregulation in cancer patients compared to healthy controls: miR-143-3p, miR-223-3p, miR-451a, miR-4516 and miR-151a-5p. The combination of six exomiRs resulted in a panel with superior diagnostic ability (p < 0.001; ROC-AUC = 0.805; 95% CI: 0.726–0.884) in distinguishing cancer patients from HDs. A model consisting of miR-223-3p, miR-143-3p and miR-451a could discriminate HPV-positive from -negative (p = 0.003; ROC-AUC = 0.939), and a model of miR-4516, miR-143-3p, miR-16-5p and miR-451a was predictive of lymph node positivity (p < 0.001, ROC-AUC = 0.786). Multivariate Cox regression showed that a model of downregulated miR-16-5p and upregulated miR-451a was significantly associated with poorer survival (p = 0.023). Conclusions: This study indicates the future potential of exomiRs as diagnostic and prognostic liquid biopsy markers for vulvar cancer. Full article

(This article belongs to the Special Issue Novel Approaches in the Management of Gynecological Cancers)

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17 pages, 1566 KB

Open AccessSystematic Review

A Systematic Review of Cutaneous Involvement in Metastatic Bone Sarcomas: Insights from 102 Reported Cases

by Nikolaos Sideris, Efstratios Vakirlis and Elena Sotiriou

Cancers 2026, 18(3), 437; https://doi.org/10.3390/cancers18030437 - 29 Jan 2026

Abstract

Background/Objectives: Cutaneous metastases from primary bone sarcomas are exceedingly rare and poorly characterized, often posing diagnostic challenges due to their atypical presentation. This systematic review aimed to describe the clinical patterns, temporal relationships, and prognostic implications of cutaneous metastases across major bone sarcoma [...] Read more.

Background/Objectives: Cutaneous metastases from primary bone sarcomas are exceedingly rare and poorly characterized, often posing diagnostic challenges due to their atypical presentation. This systematic review aimed to describe the clinical patterns, temporal relationships, and prognostic implications of cutaneous metastases across major bone sarcoma histologies. Methods: A comprehensive literature search was conducted to identify all reported cases of cutaneous metastases from osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. Data on patient demographics, primary tumor site, cutaneous lesion characteristics, latency periods, synchronous metastases, morphology, and clinical outcome were extracted and analyzed descriptively. Results: 102 cases were identified, with chordoma representing the most frequent histology. Cutaneous metastases showed histology-specific patterns: osteosarcoma and Ewing sarcoma typically presented with multiple lesions in the context of widespread systemic disease and poor prognosis, whereas chordoma more often exhibited solitary or skin-dominant metastases with longer latency and occasional favorable outcomes, including complete responses after local treatment. Conclusions: Cutaneous metastases in bone sarcomas display heterogeneous behavior, with chordoma demonstrating a more indolent and potentially manageable pattern compared to other histologies. Increased clinical awareness is essential to avoid diagnostic delays and optimize management. Full article

(This article belongs to the Special Issue Cutaneous Metastases: State-of-the-Art Research and Management)

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33 pages, 3892 KB

Open AccessReview

Chemoprevention in Skin Cancer: What Advice?

by Ariadna Ortiz-Brugués, Carmen Orte Cano, Lluis Corbella, Francesc Alamon-Reig, Ignasi Martí-Martí, Maria Ayguasanosa-Avila, Marc Hernández-Santacana, Priscila Giavedoni, Paula Aguilera and Cristina Carrera

Cancers 2026, 18(3), 436; https://doi.org/10.3390/cancers18030436 - 29 Jan 2026

Abstract

The incidence of melanoma and non-melanoma skin cancers (NMSCs) is increasing worldwide. While NMSCs are more common, melanoma remains the most challenging because of its higher aggressiveness. Although the use of sunscreens is key in high-risk populations, it provides limited protection, which highlights [...] Read more.

The incidence of melanoma and non-melanoma skin cancers (NMSCs) is increasing worldwide. While NMSCs are more common, melanoma remains the most challenging because of its higher aggressiveness. Although the use of sunscreens is key in high-risk populations, it provides limited protection, which highlights the need for alternative solutions. In this review, we discuss current evidence on chemopreventive therapies, as well as their efficacy and adverse events, including immunocompetent and immunosuppressed patients. Acitretin, nicotinamide, 5-fluorouracil, and photodynamic therapy have shown overall promising results in actinic keratosis and squamous cell carcinoma. Nevertheless, more research is needed to establish their efficacy, particularly in melanoma, Merkel cell carcinoma, and cutaneous lymphoma, due to their higher mortality rates. Full article

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

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12 pages, 1819 KB

Open AccessArticle

Single-Cell Comparison of Small Intestinal Neuroendocrine Tumors and Enterochromaffin Cells from Two Patients

by Fredrik Axling, Elham Barazeghi, Per Hellman, Olov Norlén, Samuel Backman and Peter Stålberg

Cancers 2026, 18(3), 435; https://doi.org/10.3390/cancers18030435 - 29 Jan 2026

Abstract

Background: Several studies have attempted to identify the initiating drivers of small intestinal neuroendocrine tumor (SI-NET) development and the molecular mechanisms underlying their progression and metastatic spread. Previous gene expression studies have used bulk microarrays or RNA sequencing to compare tumor tissue with [...] Read more.

Background: Several studies have attempted to identify the initiating drivers of small intestinal neuroendocrine tumor (SI-NET) development and the molecular mechanisms underlying their progression and metastatic spread. Previous gene expression studies have used bulk microarrays or RNA sequencing to compare tumor tissue with normal intestinal mucosa. However, the intestine comprises multiple distinct cell types, and bulk analyses are limited by this cellular heterogeneity, which can confound tumor-specific signals. Methods: We performed single-cell RNA sequencing on primary SI-NETs and paired normal mucosa from two patients to directly compare tumor cells with their cells of origin, the enterochromaffin (EC) cells. To minimize type I errors, we applied a two-step validation strategy by overlapping differentially expressed genes with an external single-cell dataset and cross-referencing candidate genes for enteroendocrine expression in the Human Protein Atlas. Results: For further distinction and characterization, ECs were subdivided into serotonergic and non-serotonergic clusters. This analysis revealed that the SI-NET cells are transcriptionally more similar to serotonergic ECs, consistent with serum metabolite profiles derived from clinical parameters. Our analyses uncovered a loss-of-expression program characterized by regulators of epithelial differentiation and in parallel, a gain-of-expression program displayed neuronal signaling gene induction, implicating functional reprogramming toward neuronal-like properties. Together, these specific losses and gains suggest that our patient-derived SI-NETs undergo adaptation through both loss of enteroendocrine functions and acquisition of neurobiological-promoting signaling pathways. Conclusions: These findings nominate candidate drivers for further functional validation and highlight potential therapeutic strategies in our patient cohort, including restoring suppressed Notch signaling and targeting aberrant neuronal signaling networks. However, even with a two-step validation procedure, the modest cohort size limits statistical power and generalizability, particularly for the proposed association to a serotonergic phenotype. Larger, multi-patient single-cell studies are required to confirm these mechanisms and establish their clinical relevance. Full article

(This article belongs to the Section Cancer Pathophysiology)

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16 pages, 3175 KB

Open AccessArticle

Laboratory Evaluation of Peripheral Blood Involvement in Mycosis Fungoides and Sézary Syndrome: Evolution of Flow Cytometry and Morphology Quantification and Interpretation

by Lucy Fu, Payton Trimark, Yijie Liu, Hamza Tariq, Qing Chen, Yi-Hua Chen, Juehua Gao, Barina Aqil, Joan Guitart and Kristy Wolniak

Cancers 2026, 18(3), 434; https://doi.org/10.3390/cancers18030434 - 29 Jan 2026

Abstract

Background/Objectives: Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas (CTCLs) with variable clinical outcomes. Peripheral blood (PB) involvement in MF/SS is an independent predictor of prognosis. Accurate laboratory determination of PB involvement by MF/SS cells, however, is an ongoing [...] Read more.

Background/Objectives: Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas (CTCLs) with variable clinical outcomes. Peripheral blood (PB) involvement in MF/SS is an independent predictor of prognosis. Accurate laboratory determination of PB involvement by MF/SS cells, however, is an ongoing challenge. Both flow cytometry (FC) and morphology-based quantification are limited by the overlap of CTCL cells and reactive T-cells. This study looks at the optimization over time of CTCL blood burden evaluation. Methods: This retrospective study reviews CTCL blood assessment at Northwestern Memorial Hospital from 2012 to 2021. Test ordering and reporting practices for morphology-based Sézary cell counts and FC were evaluated. For each assay, quantitative and qualitative results were analyzed and compared including percentages and absolute counts of abnormal T-cell populations and pathologist interpretations. Results: A total of 514 patients were evaluated, with increasing numbers of both tests ordered over time. FC quantitative metrics showed a moderate to high correlation with morphology metrics, especially for absolute CD4+/CD7− counts (correlation coefficient = 0.901, p-value < 0.001). Qualitative pathologist interpretations had moderate agreement between methods (kappa = 0.58). The recent addition of TRBC1 clonality assessment to our FC assay further optimizes the evaluation for CTCL blood burden. Conclusions: Flow cytometry offers a reliable approach for blood staging in MF/SS, and morphologic assessment may be redundant. This study provides a foundation for designing a new FC approach with TRBC1. This comprehensive review of the evolution of our laboratory practices may serve as a guide for other institutions with similar clinical needs. Full article

(This article belongs to the Special Issue The Role of Flow Cytometry in Hematologic Malignancies)

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16 pages, 249 KB

Open AccessArticle

An Algorithmic Approach for Quantitative Determination of Microsatellite Status in NGS-Based Cancer Diagnostics

by Josefin Männlein and William Sterlacci

Cancers 2026, 18(3), 433; https://doi.org/10.3390/cancers18030433 - 29 Jan 2026

Abstract

Purpose: To develop a transparent and adaptable methodological framework for the analysis of microsatellite status using Next Generation Sequencing (NGS), addressing current limitations in clinical implementation. Methods: Microsatellite status was assessed using NGS with a custom-designed panel. The approach was validated against polymerase [...] Read more.

Purpose: To develop a transparent and adaptable methodological framework for the analysis of microsatellite status using Next Generation Sequencing (NGS), addressing current limitations in clinical implementation. Methods: Microsatellite status was assessed using NGS with a custom-designed panel. The approach was validated against polymerase chain reaction (PCR) and immunohistochemistry (IHC) results in a cohort of 32 patients with various tumor entities. A Python-based analysis pipeline was developed to process raw sequencing data and quantify mutational burden within microsatellite regions. Results: The proposed method demonstrated 100% concordance with PCR and 90.32% concordance with IHC results. The framework enabled quantitative assessment of microsatellite instability. Conclusions: This proof-of-concept study demonstrates reliable determination of microsatellite status. The transparent and panel-adaptable framework offers flexibility for clinical implementation and provides a robust foundation for further validation in larger cohorts and across diverse tumor entities. Full article

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

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14 pages, 585 KB

Open AccessReview

Uveal Melanoma: Biology, Prognostication, and Emerging Therapies to Outsmart an Immune-Cold Melanoma

by Danielle Brazel and Elizabeth Buchbinder

Cancers 2026, 18(3), 432; https://doi.org/10.3390/cancers18030432 - 29 Jan 2026

Abstract

Uveal melanoma (UM) is a rare but highly aggressive malignancy arising from melanocytes of the uveal tract. Despite high local control rates for primary disease, half of patients ultimately develop metastatic disease with historically dismal outcomes. Unlike cutaneous melanoma, UM is characterized by [...] Read more.

Uveal melanoma (UM) is a rare but highly aggressive malignancy arising from melanocytes of the uveal tract. Despite high local control rates for primary disease, half of patients ultimately develop metastatic disease with historically dismal outcomes. Unlike cutaneous melanoma, UM is characterized by a low tumor mutational burden, distinct driver mutations, and an immunosuppressive tumor microenvironment which together limit the efficacy of immune checkpoint inhibitors. Over the past decade, major advancements in molecular classification, prognostication, and therapeutic development have reshaped the clinical landscape for some patients with UM. This review synthesizes the current understanding of UM epidemiology, characteristics, prognostic biomarkers, immune biology, and contemporary management for both localized and metastatic disease. While survival gains remain modest, the rapid expansion of biologically informed and immune-based strategies offers cautious optimism for improving outcomes in this historically treatment-refractory disease. Full article

(This article belongs to the Special Issue Precision Oncology for Rare Skin Cancers)

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13 pages, 441 KB

Open AccessReview

CT-Assessed Body Composition as Predictor of Post-Operative Complications in Lung Cancer Patients

by Stefania Rizzo and Francesco Petrella

Cancers 2026, 18(3), 431; https://doi.org/10.3390/cancers18030431 - 29 Jan 2026

Abstract

Body composition, specifically the quantification of skeletal muscle and adipose tissue using preoperative computed tomography (CT) imaging, is a clinically significant predictor of postoperative complications after lung cancer surgery. The main features of CT-derived body composition analysis are: skeletal muscle index, muscle density, [...] Read more.

Body composition, specifically the quantification of skeletal muscle and adipose tissue using preoperative computed tomography (CT) imaging, is a clinically significant predictor of postoperative complications after lung cancer surgery. The main features of CT-derived body composition analysis are: skeletal muscle index, muscle density, adipose tissue quantification and automated or semi-automated segmentation. Low skeletal muscle mass (sarcopenia) independently increases the risk of perioperative complications, including respiratory complications, and is associated with longer hospital length of stay and worse long-term survival. Sarcopenic obesity—characterized by low muscle mass in the context of high adiposity—further elevates complication risk and prolongs recovery. CT-derived measures such as muscle cross-sectional area, muscle density, and adipose tissue distribution (visceral, subcutaneous, and intramuscular) provide more precise risk stratification than BMI alone. Skeletal muscle area and density are inversely correlated with postoperative complications and recurrence risk; patients with lower muscle mass and density experience more adverse outcomes. In men, age and reduced skeletal muscle area are particularly strong predictors of complications after pneumonectomy. Obesity, when not accompanied by sarcopenia or myosteatosis, may confer a survival advantage—the so-called “obesity paradox”—but this protective effect is lost in patients with low muscle mass or poor muscle quality. Systemic inflammation and nutritional status further modulate the impact of body composition on surgical risk. This review highlights the critical role of CT-derived body composition analysis in predicting postoperative outcomes following lung cancer surgery. Full article

(This article belongs to the Special Issue The Emerging Role of Multiplexed Imaging for Cancer Diagnosis and Therapy (2nd Edition))

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40 pages, 2561 KB

Open AccessReview

LncRNAs at the Crossroads of Precision Nutrition and Cancer Chemoprevention

by Camelia Munteanu, Revathy Nadhan, Sabina Turti, Eftimia Prifti, Larisa Achim, Sneha Basu, Alessandra Ferraresi, Ji Hee Ha, Ciro Isidoro and Danny N. Dhanasekaran

Cancers 2026, 18(3), 430; https://doi.org/10.3390/cancers18030430 - 29 Jan 2026

Abstract

Cancer remains a leading cause of morbidity and mortality worldwide, and effective strategies for cancer prevention are urgently needed to complement therapeutic advances. While dietary factors are known to influence cancer risk, the molecular mechanisms that mediate inter-individual responses to nutritional exposures remain [...] Read more.

Cancer remains a leading cause of morbidity and mortality worldwide, and effective strategies for cancer prevention are urgently needed to complement therapeutic advances. While dietary factors are known to influence cancer risk, the molecular mechanisms that mediate inter-individual responses to nutritional exposures remain poorly defined. Emerging evidence identifies long non-coding RNAs (lncRNAs) as pivotal regulators of gene expression, chromatin organization, metabolic homeostasis, immune signaling, and cellular stress responses, the core processes that drive cancer initiation and progression and are highly sensitive to nutritional status. In parallel, advances in precision nutrition have highlighted how variability in genetics, metabolism, microbiome composition, and epigenetic landscapes shape dietary influences on cancer susceptibility. This review integrates these rapidly evolving fields by positioning lncRNAs as molecular conduits that translate dietary exposures into transcriptional and epigenetic programs governing cancer development, progression, and therapeutic vulnerability. We provide mechanistic evidence demonstrating how dietary bioactive compounds and micronutrients, including polyphenols [such as curcumin, resveratrol, epigallocatechin gallate (EGCG)], flavonoids, alkaloids such as berberine, omega-3 (ω-3) fatty acids, folate, vitamin D, probiotic metabolites (such as butyrate and propionate), and trace elements (such as selenium and zinc), modulate oncogenic and tumor-suppressive lncRNAs. These nutrient–lncRNA interactions influence cancer-relevant pathways controlling proliferation, epithelial–mesenchymal transition (EMT), inflammation, oxidative stress, and metabolic rewiring. We further discuss emerging lncRNA signatures that reflect nutritional and metabolic states, their potential utility as biomarkers for individualized dietary interventions, and their integration into liquid biopsy platforms. Leveraging multi-omics datasets and systems biology, we outline AI-driven frameworks to map nutrient–lncRNA regulatory networks and identify targetable nodes for cancer chemoprevention. Finally, we address translational challenges, including compound bioavailability, inter-individual variability, and limited clinical validation, and propose future directions for incorporating lncRNA profiling into precision nutrition-guided cancer prevention trials. Together, these insights position lncRNAs at the nexus of diet and cancer biology and establish a foundation for mechanistically informed precision nutrition strategies in cancer chemoprevention. Full article

(This article belongs to the Special Issue Cancer Causes and Control)

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2 pages, 165 KB

Open AccessComment

Comment on Karaulic et al. Exploring Novel Applications: Repositioning Clinically Approved Therapies for Medulloblastoma Treatment. Cancers 2025, 17, 3659

by Rafael Roesler, Mariane da Cunha Jaeger, Caroline Brunetto de Farias and Amanda Thomaz

Cancers 2026, 18(3), 429; https://doi.org/10.3390/cancers18030429 - 29 Jan 2026

Abstract

We read with great interest the recent study by Karaulic et al [...] Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Malignant Nervous System Cancers)

26 pages, 2852 KB

Open AccessReview

Targeting Pathways Implicated in Cholesterol Metabolism for Novel Cancer Therapy

by Yi Zhou, Vishakha Sharma, Xiaoyu Li, Rajeev K. Singla, Ankush Kumar, Ashishkumar Kyada, Suhas Ballal, Deepak Nathiya, Apurva Koul, Mohammad Khalid, Monica Gulati, Sandeep Arora, Tapan Behl, Joachim Kavalakatt, Bairong Shen and Anupam Bishayee

Cancers 2026, 18(3), 428; https://doi.org/10.3390/cancers18030428 - 28 Jan 2026

Abstract

Cholesterol acts as a metabolic cue that reshapes diverse signaling networks, including hedgehog and several sterol-regulated pathways orchestrated by key proteins, including sterol regulatory element-binding protein 2 (SREBP2), sterol O-acyltransferase 1 (SOAT1), Niemann–Pick type C1 (NPC1), and proprotein convertase subtilisin/kexin type 9 (PCSK9). [...] Read more.

Cholesterol acts as a metabolic cue that reshapes diverse signaling networks, including hedgehog and several sterol-regulated pathways orchestrated by key proteins, including sterol regulatory element-binding protein 2 (SREBP2), sterol O-acyltransferase 1 (SOAT1), Niemann–Pick type C1 (NPC1), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Research over the past decade has highlighted cholesterol metabolism as a key modulator of cancer development and a promising therapeutic target. By integrating mechanistic and translational evidence, this review seeks to clarify how cholesterol metabolism interfaces with oncogenic signaling and set directions for future investigation. Accumulating preclinical and clinical data suggest that dysregulated cholesterol levels, often associated with high-fat diets, may contribute to tumorigenesis and malignant transformation. Implicated pathways, such as SREBP, NPC1, PCSK9, and SOAT1, orchestrate various processes of lipid metabolism, including cholesterol synthesis, esterification, receptor degradation, and transport, that harbor a tumorigenic environment and promote oncogenic processes. Additionally, these enzymes and corresponding pathways provide a promising direction for developing metabolism-oriented anticancer strategies. Cholesterol metabolism dysregulation serves as a major avenue for cancer signaling and growth, but studies also highlight key molecular mechanisms and targets for future treatments. Future studies should focus on expanding studies into further cancer types, investigating combination therapies, and developing novel inhibitors of key molecular targets. Full article

(This article belongs to the Special Issue Discovery and Development of New Anticancer Drugs and Delivery Systems: Special Emphasis on Artificial Intelligence, Machine-Learning, and Big Data Analysis)

19 pages, 321 KB

Open AccessReview

Detecting Occult Sentinel Node Metastases in HNSCC: The Emerging Role of lncRNAs as Biomarkers and Future Perspectives for USgFNAB Molecular Profiling

by Boštjan Lanišnik, Janez Mohorko and Uroš Potočnik

Cancers 2026, 18(3), 427; https://doi.org/10.3390/cancers18030427 - 28 Jan 2026

Abstract

Background: Accurate detection of cervical lymph node metastases is a critical determinant of prognosis and treatment planning in head and neck squamous cell carcinoma (HNSCC). Although ultrasound-guided fine-needle aspiration biopsy (USgFNAB) is widely used as a minimally invasive diagnostic tool, its sensitivity for [...] Read more.

Background: Accurate detection of cervical lymph node metastases is a critical determinant of prognosis and treatment planning in head and neck squamous cell carcinoma (HNSCC). Although ultrasound-guided fine-needle aspiration biopsy (USgFNAB) is widely used as a minimally invasive diagnostic tool, its sensitivity for detecting occult metastases remains limited. Current preoperative staging modalities are further constrained by operator dependency and suboptimal specificity in early-stage disease. Integration of molecular diagnostics, particularly the analysis of long non-coding RNAs (lncRNAs), represents a promising strategy to enhance diagnostic accuracy. Objective: This review synthesizes the current evidence on lncRNA expression profiles in HNSCC, with an emphasis on their association with lymph node metastasis and potential application in FNAB-derived material for pre-treatment staging. Methods: A structured literature search was conducted, focusing on studies evaluating lncRNA expression profiles in HNSCC and their relevance to lymph node metastasis, with a particular focus on the feasibility of analysis of USgFNAB samples. Results: Multiple lncRNAs, including HOTAIR, MALAT1, UCA1, TUG1, AFAP1-AS1, H19, MEG3, and ADAMTS9-AS2, have been implicated in metastatic progression through their involvement in diverse mechanisms such as epithelial-to-mesenchymal transition, chromatin remodeling, angiogenesis, and pre-metastatic niche formation. Elevated expression of several of these transcripts correlates with adverse clinicopathological features, including advanced tumor stage, extranodal extension, and reduced survival. However, no studies have profiled lncRNA expression in matched primary tumors and metastatic lymph nodes, and transcriptomic analysis of FNAB samples remains largely unexplored in HNSCC. Conclusions: lncRNAs represent promising molecular biomarkers for enhancing the sensitivity and specificity of USgFNAB in detecting occult cervical metastases. Future research should prioritize paired tumor–node lncRNA profiling, validation of FNAB-based molecular assays, and integration of multi-omics data for predictive modeling. Overall, integrating lncRNA analysis into ultrasound-guided fine-needle aspiration biopsy may enhance the detection of occult nodal metastases in head and neck squamous cell carcinoma and support more accurate nodal staging in clinically node-negative patients. Full article

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

10 pages, 733 KB

Open AccessArticle

Generalization of the Conformity Index for Multi-Target Radiotherapy Plans

by Yong Sang, Jun Dang, Jianan Wu, Yanling Wu, Enzhuo Quan and Jianrong Dai

Cancers 2026, 18(3), 426; https://doi.org/10.3390/cancers18030426 - 28 Jan 2026

Abstract

Background and Purpose: Based on the distortion of the current conformity index (CI) formula in handling multi-target plans, the

V_{T V}

parameter in the current CI formula has been redefined to more accurately calculate the CI value of multi-target plans, providing a [...] Read more.

Background and Purpose: Based on the distortion of the current conformity index (CI) formula in handling multi-target plans, the

V_{T V}

parameter in the current CI formula has been redefined to more accurately calculate the CI value of multi-target plans, providing a reference for clinical applications. Methods and Materials: Considering the limitations of the current

V_{T V}

calculation formula in CI proposed by van’t Riet and Paddick, a new

V_{T V}

has been defined to better reflect the true conformity of the target volume in multi-target planning. We selected 15 breast cancer (BC) plans with PTVsc and PTVcw as the target volumes, and 15 nasopharyngeal carcinoma (NPC) plans with PTVp, PTVn, PTVrpn, PTV1, and PTV2 as target volumes.

V_{T V}^{n e w}

and

C I_{n e w}

were calculated using the proposed formulas, while

V_{T V}^{o l d}

and

C I_{o l d}

were calculated using traditional formulas based on van’t Riet and Paddick. A paired, two-tailed Wilcoxon signed-rank test was conducted to compare

V_{T V}^{n e w}

with

V_{T V}^{o l d}

, and

C I_{n e w}

with

C I_{o l d}

across all target volumes. Pearson’s correlation analysis was performed between

C I_{n e w}

and

C I_{o l d}

. Results: For BC, the

V_{T V}

values calculated by the two methods for PTVsc and PTVcw showed statistically significant differences; the values calculated in this study were significantly lower than those calculated by van’t Riet and Paddick (p < 0.05). Consequently, the

C I_{n e w}

values for BC were significantly higher than

C I_{o l d}

. These results were consistent with those for PTVp, PTVn, PTVrpn, and PTV2 in NPC. For PTV1 in NPC, the results calculated by the two formulas were identical. Conclusions: The new

V_{T V}

calculation formula eliminates the influence of dose spillage from adjacent targets, retaining only the prescription dose range of the specific target under analysis. This makes the calculated CI more reflective of true conformity compared to traditional formulas. We recommend using the proposed formula to calculate CI values for multi-target plans such as those for BC and NPC. Full article

(This article belongs to the Special Issue Image-Assisted High-Precision Radiation Oncology)

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