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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)
Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology published semimonthly online. The North-East German Society for Gynecological Oncology (NOGGO), Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and more 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)
Latest Articles
Robotic Rectus Muscle Flap Reconstruction After Pelvic Exenteration in Gynecological Oncology: Current and Future Perspectives—A Narrative Review
Cancers 2026, 18(3), 375; https://doi.org/10.3390/cancers18030375 (registering DOI) - 25 Jan 2026
Abstract
Background/Objectives: Pelvic exenteration is a radical procedure performed for recurrent gynecologic cancers. The goal of exenteration is to prolong survival, but this procedure also results in extensive tissue loss and consequently high morbidity. Reconstruction using vascularized flaps, particularly the VRAM flap, is
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Background/Objectives: Pelvic exenteration is a radical procedure performed for recurrent gynecologic cancers. The goal of exenteration is to prolong survival, but this procedure also results in extensive tissue loss and consequently high morbidity. Reconstruction using vascularized flaps, particularly the VRAM flap, is crucial to restoring pelvic integrity and decreasing complications resulting from extensive tissue loss. With the rise of minimally invasive surgery, the traditionally open abdominal approach to exenteration and reconstruction can now be performed with the assistance of robotic platforms. This review aims to summarize available evidence, describe techniques, and propose future directions for robotic rectus flap reconstruction after pelvic exenteration. Methods: This narrative review was conducted following the SANRA guidelines for narrative synthesis. A comprehensive search of PubMed, Embase, Scopus, and Web of Science was conducted for studies published between January 2000 and November 2025 on pelvic exenteration followed by robotic rectus abdominis flap reconstruction in gynecologic oncology. Eligible studies were retrospective or prospective reports, technical descriptions, case series, or comparative analyses. Non-robotic techniques and animal studies were excluded. Although the primary focus was gynecologic oncology, technically relevant studies from other oncologic disciplines were included when the reconstructive approach was directly applicable to pelvic exenteration. Extracted data included patient demographics, surgical details, and perioperative and oncologic outcomes. Results: The literature search identified primarily case reports and small single-center series describing robot-assisted rectus muscle-based flap reconstruction after pelvic exenteration. Reported cases demonstrated technical feasibility and successful flap harvest using robotic platforms, with adequate pelvic defect coverage. Potential benefits, such as reduced wound morbidity and preservation of a minimally invasive workflow, have been described. However, patient numbers were small, techniques varied, and standardized outcome measures or comparative data with open approaches were lacking. Conclusions: Robotic rectus flap reconstruction represents a promising advancement in pelvic exenteration surgery, potentially reducing morbidity and improving recovery. Further research, including multicenter prospective studies, is needed to validate these findings and establish standardized protocols.
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(This article belongs to the Special Issue Radical Pelvic Surgery and Reconstructive Innovations in Pelvic Oncology)
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Lipidemic Profile of Patients with Non-Small Cell Lung Cancer and Its Association with Driver Mutations: A Tertiary Center Retrospective Study
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Maria Lagadinou, Dimitrios Efthymiou, Fotios Sampsonas, Prokopis Karidis, Ioanna Marlafeka, Eirini Adamopoulou, Christos Michailides, Pinelopi Bosgana, Ourania Papaioannou, Emmanouil Psarros, Panagiota Tsiri, Vasilina Sotiropoulou, Matthaios Katsaras, Vasiliki Tzelepi, Argyrios Tzouvelekis and Markos Marangos
Cancers 2026, 18(3), 374; https://doi.org/10.3390/cancers18030374 (registering DOI) - 25 Jan 2026
Abstract
Background: Altered lipid metabolism has been reported in several malignancies, but its clinical relevance in non-small cell lung cancer (NSCLC) remains uncertain. This study aimed to compare serum lipid parameters between NSCLC patients and healthy controls and to explore their association with histological
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Background: Altered lipid metabolism has been reported in several malignancies, but its clinical relevance in non-small cell lung cancer (NSCLC) remains uncertain. This study aimed to compare serum lipid parameters between NSCLC patients and healthy controls and to explore their association with histological subtype and selected driver mutations. Methods: We retrospectively analyzed serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) in patients diagnosed with adenocarcinoma or squamous cell carcinoma from 2021 to 2024, alongside a control group of 100 healthy individuals. Statistical comparisons were performed using appropriate parametric or nonparametric tests after normality assessment (Shapiro–Wilk), and p-values were adjusted using the Benjamini–Hochberg false discovery rate (FDR). Results: A total of 160 NSCLC patients were included. Most were male (75.5%) and current or former smokers (96.1%), with a mean age of 70.4 ± 10.3 years. Squamous cell carcinoma was the predominant subtype (64.4%). Hypocholesterolemia was observed in 59.9% of patients, while hypercholesterolemia was less frequent (40.1%). Compared with controls, patients had significantly lower HDL levels (p = 0.007, FDR-adjusted p = 0.024), while other lipid markers showed no statistically significant differences after correction for multiple testing. Differences between adenocarcinoma and squamous cell carcinoma were not statistically significant. Squamous cell carcinoma patients had higher TG but lower TC, LDL, and HDL levels compared with adenocarcinoma. A negative correlation between TG and ROS1 expression remained significant (r = −0.223, FDR-adjusted p = 0.004). Conclusions: In this retrospective, real-world cohort, only HDL levels demonstrated a robust difference between NSCLC patients and controls. Observed associations should be interpreted cautiously due to potential confounding factors and incomplete clinical data inherent to retrospective analyses. Prospective studies are needed to clarify whether lipid alterations play a biological or prognostic role in NSCLC.
Full article
(This article belongs to the Special Issue Advances in Interventional Oncologic Therapies)
Open AccessArticle
Naloxegol, an Oral Peripherally Acting Opioid Receptor Antagonist, Administered Concurrently with First-Line Systemic Therapy for Advanced Lung Adenocarcinoma (Alliance A221504): A Feasibility and Safety Study
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Pankaj Gupta, Kalpna Gupta, Travis Dockter, Elizabeth Harlos, Selina Chow, Niveditha Subbiah, Kathryn J. Ruddy, Lyudmila Bazhenova, Shelby Terstriep, Chao H. Huang, Robert A. Kratzke, Everett E. Vokes and Charles L. Loprinzi
Cancers 2026, 18(3), 373; https://doi.org/10.3390/cancers18030373 (registering DOI) - 25 Jan 2026
Abstract
Background: Mu opioid receptors (MORs) in peripheral tissues mediate adverse effects of opioids that impair health-related quality of life (HRQoL) and may stimulate cancer progression via mitogenic signaling. Naloxegol, a peripherally acting MOR antagonist (PAMORA), is approved for opioid-induced constipation. Safety and
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Background: Mu opioid receptors (MORs) in peripheral tissues mediate adverse effects of opioids that impair health-related quality of life (HRQoL) and may stimulate cancer progression via mitogenic signaling. Naloxegol, a peripherally acting MOR antagonist (PAMORA), is approved for opioid-induced constipation. Safety and efficacy of naloxegol have not been evaluated concurrently with systemic cancer therapy. Methods: We conducted a randomized, double-blind, placebo-controlled trial of naloxegol in patients with advanced lung adenocarcinoma starting first-line systemic therapy. Results: Only 50 patients were enrolled; the trial was terminated early due to slow accrual. Two of the three components of the feasibility primary endpoint were not met (accrual and PRO completion). At 6 months, FACT-L emotional well-being was better with naloxegol (p = 0.0113). There were trends towards better Trial Outcome Index (p = 0.0505) and physical well-being (p = 0.0628) with naloxegol. Bowel function favored naloxegol for constipation (p = 0.0223), rectal pain during defecation (p = 0.0075), and abdominal pain from constipation (p = 0.0113). Adverse event frequency and severity, PRO-CTCAE, urinary hesitancy, pain scores, and progression-free and overall survival were comparable between naloxegol and placebo. Conclusions: Naloxegol appears to be safe and tolerable, with a signal of improved HRQoL and previously unappreciated benefit for emotional well-being, without adverse clinical outcomes. Our findings should be confirmed in larger studies. ClinicalTrials.gov ID: NCT03087708.
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(This article belongs to the Section Cancer Therapy)
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Open AccessSystematic Review
Ex Vivo Organotypic Brain Slice Models for Glioblastoma: A Systematic Review
by
Cateno C. T. Petralia, Agata G. D’amico, Velia D’Agata, Giuseppe Broggi and Giuseppe M. V. Barbagallo
Cancers 2026, 18(3), 372; https://doi.org/10.3390/cancers18030372 (registering DOI) - 25 Jan 2026
Abstract
Background/Objective: This systematic review aims to evaluate ex vivo brain slice models in glioblastoma (GBM) research, with a specific focus on tumour invasion, tumour–microenvironment interactions, and therapeutic response. Methods: A systematic search looking for studies employing ex vivo organotypic brain slice models in
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Background/Objective: This systematic review aims to evaluate ex vivo brain slice models in glioblastoma (GBM) research, with a specific focus on tumour invasion, tumour–microenvironment interactions, and therapeutic response. Methods: A systematic search looking for studies employing ex vivo organotypic brain slice models in GBM research was conducted across multiple databases (January 2010–July 2025) in accordance with PRISMA guidelines. The study was registered in PROSPERO database (CRD420251138341). Inclusion criteria encompassed patient-derived brain slices, hybrid rodent–human slice co-cultures, and microfluidic-integrated ex vivo platforms designed to assess tumour invasion, microenvironmental interactions and therapeutic responses. Exclusion criteria included reviews, abstracts, conference proceedings, in vivo-only studies, purely in vitro models without organotypic integration, and studies not focused on GBM. Results: Twenty-six studies met the inclusion criteria. Among these, 18/26 (69%) investigated GBM invasion, 18/26 (69%) evaluated therapeutic responses, and 5/26 (19%) examined tumour–microenvironment interactions, with several studies spanning multiple domains. Across platforms, organotypic slices consistently recapitulated key features of GBM biology—including perivascular and white-matter-aligned invasion, stromal–immune interactions, and patient-specific drug sensitivity—while engineered systems enhanced perfusion and exposure control. Methodological variability, particularly regarding slice preparation, oxygenation and viability assessment, limits direct comparability between studies. Conclusions: Organotypic brain slice models represent an extremely relevant tool for translational investigations of GBM biology and treatment response. However, substantial methodological heterogeneity together with limited standardisation hamper reproducibility and cross-study validation. Future work should focus on enhancing reproducibility and harmonising protocols to support the development of clinically meaningful precision oncology strategies.
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(This article belongs to the Special Issue Novel Insights into Glioblastoma and Brain Metastases (2nd Edition))
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Open AccessArticle
Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro β-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer
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Vanessa Rodriguez, Annacandida Villani, Margarida Sénica, Concetta Panebianco, Valerio Pazienza and Ana Preto
Cancers 2026, 18(3), 369; https://doi.org/10.3390/cancers18030369 (registering DOI) - 25 Jan 2026
Abstract
Background: Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota’s role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro β-carboline
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Background: Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota’s role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro β-carboline carboxylic acid (THC), in targeting some hallmark traits of PC and CRC, both as standalone agents and in combination with standard chemotherapeutics (gemcitabine for PC and 5-fluorouracil (5-FU) for CRC). Methods: Cell viability assays and IC50 determination was assessed using either the Muse™ Count & Viability Kit or the Sulforhodamine B assay; cell death was determined by Annexin V/Propidium Iodide and cell cycle assessed by Propidium Iodide was analyzed by flow cytometry. Results: Here, we found that NAC selectively reduced the viability of PC cells BxPC-3 without triggering apoptosis, while effectively inducing apoptosis in PC cells Panc-1 and in CRC cell lines. THC exhibited stronger anticancer activity, inhibiting proliferation and promoting apoptosis in all tested PC and CRC cells, even at lower concentrations. Combination treatments yielded promising enhancement effects. NAC enhanced the cytotoxicity of gemcitabine in Panc-1 cells through increased apoptosis. NAC, when combined with 5-FU, also increased apoptosis of CRC cells. THC further potentiated gemcitabine’s impact on Panc-1 cells by increasing apoptosis and by inducing cell cycle changes in BxPC-3. In the CRC model, THC co-treatment with 5-FU reduced cell viability and increased apoptosis in all cells. Conclusions: These findings provide preliminary in vitro evidence supporting the potential of integrating microbiota-derived postbiotics with conventional chemotherapy both in PC and CRC.
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(This article belongs to the Special Issue Unravelling Cancer Mechanism and Developing Novel Therapeutics: An Urgent Need to Treat Cancer (2nd Edition))
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Open AccessReview
Cutaneous Adverse Effects in Patients Treated with BTK Inhibitors
by
Ewa Robak and Tadeusz Robak
Cancers 2026, 18(3), 371; https://doi.org/10.3390/cancers18030371 (registering DOI) - 24 Jan 2026
Abstract
Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The most common adverse events include cardiac arrhythmia, bleeding, infection, diarrhea, arthralgias, hypertension, and skin changes.
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Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The most common adverse events include cardiac arrhythmia, bleeding, infection, diarrhea, arthralgias, hypertension, and skin changes. Second-generation BTK inhibitors, e.g., acalabrutinib and zanubrutinib and the non-covalent BTK inhibitor pirtobrutinib, are less toxic than the first-generation BTK inhibitor ibrutinib. The most common toxic skin symptoms related to BTKi treatment include hemorrhage, bleeding events, bruising, skin ecchymoses, and contusion; they are particularly common in patients treated with ibrutinib. Other dermatologic symptoms include rash, cellulitis, skin infections, subcutaneous abscesses and peripheral edema. This article discusses the development of skin symptoms in patients with ibrutinib and newer BTK inhibitors, and summarizes their clinical and pathological characteristics. A literature search was performed using PubMed, Web of Science, and Google Scholar for articles published in English. Additional relevant publications were obtained by reviewing the references from the chosen articles.
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(This article belongs to the Special Issue Advances in Chronic Lymphocytic Leukaemia (CLL) Research)
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Open AccessArticle
Antitumor Effects of Broadleaf Vetch Against Esophageal Squamous Cell Carcinoma Through Dual Mechanisms: Suppressing EMT and Inducing Ferroptosis with Predicted Hepatorenal Toxicity—An Integrative Network Pharmacology and Toxicology Study
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Yuxuan Xing, Siao Chen, Kang Hu, Zihan Cui, Yuhan Shao, Jingfeng Zhu, Zhimeng Chen, Jun Chen, Weijun Deng, Cheng Ding and Jun Zhao
Cancers 2026, 18(3), 370; https://doi.org/10.3390/cancers18030370 (registering DOI) - 24 Jan 2026
Abstract
Background: Esophageal squamous cell carcinoma (ESCC) remains a highly lethal malignancy with limited effective treatments. Broadleaf Vetch (Vicia amoena, BV) is a traditional medicinal herb with potential anticancer properties, but its mechanisms in ESCC are not fully understood. Methods: Network pharmacology
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Background: Esophageal squamous cell carcinoma (ESCC) remains a highly lethal malignancy with limited effective treatments. Broadleaf Vetch (Vicia amoena, BV) is a traditional medicinal herb with potential anticancer properties, but its mechanisms in ESCC are not fully understood. Methods: Network pharmacology was used to identify BV-related therapeutic targets and pathways. Molecular docking validated interactions between BV components and core proteins. In vitro assays evaluated proliferation, colony formation, migration, invasion, epithelial–mesenchymal transition (EMT) markers, and ferroptosis-related indices. An ESCC xenograft model was used to assess antitumor efficacy in vivo. Results: Five major BV components and 363 ESCC-related targets were identified, highlighting the PI3K–AKT pathway and key nodes such as EGFR, AKT1, SRC, TP53, and GPX4. BV significantly inhibited ESCC cell proliferation, migration, and invasion, and reversed EMT marker expression. Ferroptosis induction was evidenced by significant Fe2+ accumulation, elevated reactive oxygen species (ROS) and malondialdehyde levels, alongside glutathione depletion. BV treatment also precipitated mitochondrial dysfunction. In parallel, BV downregulated GPX4 and SLC7A11. Notably, these changes were largely reversed by the ferroptosis inhibitor Ferrostatin-1. In vivo, BV suppressed tumor growth and regulated EMT- and ferroptosis-associated proteins in xenograft tissues. Conclusions: BV exerts dual antitumor effects in ESCC by suppressing EMT and inducing ferroptosis. These findings suggest BV may represent a potential multi-target phytotherapeutic candidate for ESCC.
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(This article belongs to the Section Cancer Drug Development)
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Dual Targeting of IDH2 and the Ubiquitin-Proteasome System Reveals a Functional Vulnerability in Breast Cancer Models
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Nariman Gharari, Elisabetta Mereu, Beatrice Luciano, Bahareh Heidari, Sylvie Mader and Roberto Piva
Cancers 2026, 18(3), 368; https://doi.org/10.3390/cancers18030368 (registering DOI) - 24 Jan 2026
Abstract
Background/Objectives: Breast cancer cells rely on both mitochondrial metabolism and proteostatic mechanisms for cell fitness. The mitochondrial enzyme IDH2 supports redox balance and biosynthesis, while the ubiquitin-proteasome system (UPS) preserves protein quality. This study aimed to determine whether inhibiting IDH2 enhances sensitivity to
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Background/Objectives: Breast cancer cells rely on both mitochondrial metabolism and proteostatic mechanisms for cell fitness. The mitochondrial enzyme IDH2 supports redox balance and biosynthesis, while the ubiquitin-proteasome system (UPS) preserves protein quality. This study aimed to determine whether inhibiting IDH2 enhances sensitivity to proteasome-targeting agents across breast cancer subtypes. Methods: A panel of human and murine breast cancer cell lines was treated with the IDH2 inhibitor AGI-6780, alone or in combination with the proteasome inhibitor carfilzomib (CFZ) or the E1 ubiquitin-activating enzyme inhibitor TAK-243. Synergy was evaluated using Bliss scoring. Apoptosis, clonogenicity, and pathway modulation were assessed through Western blotting, colony-formation assays, and reverse-phase protein array (RPPA) profiling. Results: We observed that co-targeting IDH2 and the UPS produced strong synergistic cytotoxicity in multiple breast cancer models, including in triple-negative MDA-MB-231 and 4T1 cells (Bliss > 25). Combination treatments led to pronounced apoptosis, evidenced by cleaved PARP-1 and Caspase-3 cleavage, and a marked loss of clonogenic potential. RPPA analysis revealed significant alterations in key survival and stress-response pathways, including NF-κB, PI3K-p85, Src, and p38-MAPK. Conclusions: Inhibition of IDH2 markedly enhances the cytotoxic effects of proteasome-targeting by disrupting metabolic–proteostatic balance and promoting apoptotic cell death. These findings identify a growth-inhibitory effect that may be leveraged to improve functional dependency in breast cancer, particularly in triple-negative breast cancer, which currently lacks efficient drug treatments.
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(This article belongs to the Section Molecular Cancer Biology)
Open AccessArticle
Leveraging Landmark Analysis for Tailored Surveillance in Stage I Non-Small-Cell Lung Cancer
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Giovanni Leuzzi, Federica Sabia, Matteo Calderoni, Clarissa Uslenghi, Ugo Pastorino, Alfonso Marchianò, Michele Ferrari, Alessandro Pardolesi, Daniele Lorenzini, Giuseppe Lo Russo, Claudia Proto, Arsela Prelaj and Piergiorgio Solli
Cancers 2026, 18(3), 367; https://doi.org/10.3390/cancers18030367 (registering DOI) - 24 Jan 2026
Abstract
Background: Current guidelines for NSCLC follow-up lack specific recommendations on surveillance duration. This study aims to analyze survival and surveillance data in resected stage I NSCLC. Methods: We retrospectively reviewed 759 pathological stage I NSCLC (9thTNM ed.) patients with no history
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Background: Current guidelines for NSCLC follow-up lack specific recommendations on surveillance duration. This study aims to analyze survival and surveillance data in resected stage I NSCLC. Methods: We retrospectively reviewed 759 pathological stage I NSCLC (9thTNM ed.) patients with no history of lung cancer (LC) undergoing surgery from January 2003 to December 2018. Overall survival (OS), incidence of relapse (IR), and incidence of new primary LC (NP) were analyzed. Long-term effect of follow-up beyond 5 years was assessed by landmark analysis of OS, IR, and NP at 10 years, restricted to individuals alive without relapse or NP at 5 years (5-year event-free survivors, 5y-EFSs). Results: The rates of 10-year OS, 10-year IR, NP incidence, and 5y-EFSs were, respectively, 75%, 18%, 1.1%/year, and 59.1% (449 patients). Carcinoid IA/IB (0–10%) and adenocarcinoma IA/IB without lung nodules (LNs) (8–12%) had a similarly lower risk of relapse (p = 0.5088) compared to adenocarcinoma with LNs (p = 0.0191). Similarly, carcinoid (0–0.2%/year) and adenocarcinoma without LNs (0-0.3%/year) had the same lower incidence of NP (p = 0.8062) compared to patients with LNs (p < 0.0001). The group of 5y-EFSs had a conditional 10-year OS, IR, and NP incidence of 92%, 5%, and 0.8%/year. In 5y-EFSs, 10-year OS was better in carcinoid (100%) and adenocarcinoma (94%, p = 0.0009) patients; 10-year IR was lower in stage IA (4%) vs. IB (10%, p = 0.0444), and NP was lower in patients with no pre-surgery (0.5 vs. 1.5%/year, p = 0.0147) and no post-surgery LNs (0.6 vs. 1.1%/year, p = 0.0202). Conclusions: Based on our results, we propose a tailored surveillance strategy by de-escalating follow-up for low-risk patients while maintaining intensive monitoring for high-risk individuals.
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(This article belongs to the Special Issue A New Era in the Treatment of Early-Stage Non-Small Cell Lung Cancer)
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Open AccessArticle
Outcomes for Sinonasal Undifferentiated Carcinoma (SNUC): An International Multi-Center Retrospective Cohort Study
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Jacklyn Liu, Yoko Takahashi, Umar Rehman, Mario Turri-Zanoni, Davide Mattavelli, Nicholas Counsell, Marco Ferrari, Vittorio Rampinelli, William Vermi, Davide Lombardi, Rami Saade, Ki Wan Park, Oscar Emanuel, Volker H. Schartinger, Alessandro Franchi, Carla Facco, Fausto Sessa, Simonetta Battocchio, Patrick Rene Gerhard Eriksen, Simone Kloch Bendtsen, Kathrine Kronberg Jakobsen, Mohamed el Haddouchi, Roberta Maragliano, Giedrius Lelkaitis, Anirudh Saraswathula, Raman Preet Kaur, Wojciech K. Mydlarz, Murugappan Ramanathan, Jr., Masaru Ishii, Manas Dave, Tim R. Fenton, Alison Lim, Saleh Okhovat, Gyleen Elegio, Charles Dupin, Pierre Pouvreau, Juliette Thariat, Laurence Digue, Francois-Regis Ferrand, Valerie Costes-Martineau, Claire Castain, Héloïse De Kermadec, Justin Hintze, James Paul O’Neill, Peter Lacy, Francis M. Vaz, Paul O’Flynn, David J. Howard, Paul Stimpson, Simon Wang, Gary Royle, Christopher Steele, Amrita Jay, Dawn Carnell, Martin D. Forster, David Thomson, Christian von Buchwald, Robbie Woods, Jose Luis Lllorente, Mario Hermsen, Philipp Jurmeister, David Capper, Gary L. Gallia, Joshua K. Tay, Ahmed Mohyeldin, Juan Fernandez-Miranda, Quynh-Thu Le, Robert B. West, Zara M. Patel, Jayakar V. Nayak, Peter H. Hwang, Fabio Facchetti, Piero Nicolai, Renata Ferrarotto, Jack Phan, Paolo Bossi, Paolo Castelnuovo, Antoine Moya-Plana, Benjamin Verillaud, Cathie Garnis, Andrew Thamboo, Felicia Olawuni, Eric J. Moore, Garret Choby, Devyani Lal, Neal Akhave, Diana Bell, Shirley Y. Su, Valerie J. Lund, Nyall R. London, Jr., Ehab Y. Hanna and Matt Lechneradd
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Cancers 2026, 18(3), 366; https://doi.org/10.3390/cancers18030366 (registering DOI) - 24 Jan 2026
Abstract
Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted
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Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.
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(This article belongs to the Special Issue Targeted Therapy in Head and Neck Cancer)
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Open AccessArticle
Should Super-Selective Intra-Arterial Chemoradiotherapy Be Prioritized over Surgical Resection for Locally Advanced Oral Cavity Cancer?
by
Beng Gwan Teh, Wataru Kobayashi, Kosei Kubota, Shinya Kakehata, Norihiko Narita and Yoshihiro Tamura
Cancers 2026, 18(3), 365; https://doi.org/10.3390/cancers18030365 (registering DOI) - 24 Jan 2026
Abstract
Background/Objectives: Super-selective intra-arterial chemoradiotherapy (SSIACRT) is an alternatively effective treatment for locally advanced oral cavity cancer although no comparative studies on prognosis between SSIACRT and surgical resection with or without post-operative radiotherapy (S+R) have been reported. This study aimed to compare the 5-year
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Background/Objectives: Super-selective intra-arterial chemoradiotherapy (SSIACRT) is an alternatively effective treatment for locally advanced oral cavity cancer although no comparative studies on prognosis between SSIACRT and surgical resection with or without post-operative radiotherapy (S+R) have been reported. This study aimed to compare the 5-year survival rate and Quality of Life (QoL) between S+R and SSIACRT for locally advanced oral cavity cancer. Methods: From a total of 326 patients with stage III and IV oral cavity cancer treated between 2000–2020 at a single institution, 149 patients treated with S+R and SSIACRT were analyzed by using Propensity Score Matching (PSM) method, a pseudo-randomized controlled trial, and the matched cases were retrospectively evaluated. The 5-year survival rate and QoL were evaluated using the Kaplan–Meier method and the University of Washington QoL questionnaire, respectively. Log-rank test and Cox proportional hazards model were used to compare 5-year survival rate and to assess factors affecting survival rates, respectively. Paired t-test was used to compare QoL. Results: To compare the 5-year survival rate and QoL between S+R and SSIACRT, 48 and 15 cases were matched after PSM. The 149 cases were further evaluated for covariates affecting survival rates. The 5-year disease-specific survival rate and 5-year crude survival rate were 52.4% and 44.3% for S+R and 71.3%, and 62.9% for SSIACRT, respectively. There was no statistical difference in survival rates between both treatments, based on Log-rank test analysis. Treatment method was the only independent variable that influenced survival rates. SSIACRT showed better statistical difference in QoL evaluation, specifically in appearance, activity, recreation, swallowing, speech, shoulder, taste, mood, and total score. Conclusions: Propensity score-matched analysis demonstrated survival outcomes that were comparable to, and not inferior to, S+R. However, SSIACRT was associated with superior quality-of-life outcomes compared with S+R, as shown by Cox proportional hazards modeling. These findings suggest that SSIACRT is an effective treatment option and, from a quality-of-life perspective, may be considered a preferable approach in the management of locally advanced oral cavity cancer.
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(This article belongs to the Section Cancer Survivorship and Quality of Life)
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Low-Grade Fibromyxoid Sarcoma and Related Subtypes: A Systematic Review and Pooled Analysis of 773 Cases
by
Gitte G. J. Krebbekx, Elisabeth A. Kleine, C. Dilara Savci-Heijink, Diederik T. Meijer, Donner, Robert Hemke and Floortje G. M. Verspoor
Cancers 2026, 18(3), 364; https://doi.org/10.3390/cancers18030364 - 23 Jan 2026
Abstract
Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor that often appears deceptively benign. Accurate diagnosis is challenging due to its variable morphology and low mitotic activity. This systematic review provides a comprehensive overview of LGFMS and its subtypes. Methods: A
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Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor that often appears deceptively benign. Accurate diagnosis is challenging due to its variable morphology and low mitotic activity. This systematic review provides a comprehensive overview of LGFMS and its subtypes. Methods: A systematic search of PubMed and Embase up to September 2025 identified 273 studies, complemented by four institutional cases from Amsterdam UMC. Individual patient data were pooled to analyze clinical presentation, diagnostic approaches, treatment modalities, and outcomes. Results: In total, 773 patients were included, with a median age of 35 years and equal gender distribution. Tumors were predominantly deep-seated (80%), most commonly located in the thigh or pelvis. MUC4 positivity (96%) and FUS-CREB3L2 fusion (47%) were the most consistent diagnostic markers. Surgery was the mainstay of treatment (98%), with R0 resection achieved in 36% of cases and R1 in 15%. Adjuvant therapies, including chemotherapy and radiotherapy, were rarely used and showed limited efficacy. After a median follow-up of 3.0 years, 19% developed local recurrence and 21% developed metastases. R0 resections were associated with significantly better recurrence-free survival than R1 resection (p < 0.05). Conclusions: LGFMS exhibits indolent histology but potential for late recurrence and metastasis, warranting prolonged radiological follow-up and multicenter studies to evaluate adjuvant strategies.
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(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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Open AccessArticle
Spectral Precision: The Added Value of Dual-Energy CT for Axillary Lymph Node Characterization in Breast Cancer
by
Susanna Guerrini, Giulio Bagnacci, Paola Morrone, Cecilia Zampieri, Chiara Esposito, Iacopo Capitoni, Nunzia Di Meglio, Armando Perrella, Francesco Gentili, Alessandro Neri, Donato Casella and Maria Antonietta Mazzei
Cancers 2026, 18(3), 363; https://doi.org/10.3390/cancers18030363 - 23 Jan 2026
Abstract
Background/Objectives: To develop and validate a predictive model that combines morphological features and dual-energy CT (DECT) parameters to non-invasively distinguish metastatic from benign axillary lymph nodes in patients with breast cancer (BC). Methods: In this retrospective study, 117 patients (median age,
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Background/Objectives: To develop and validate a predictive model that combines morphological features and dual-energy CT (DECT) parameters to non-invasively distinguish metastatic from benign axillary lymph nodes in patients with breast cancer (BC). Methods: In this retrospective study, 117 patients (median age, 65 years; 111 women and 6 men) who underwent DECT followed by axillary lymphadenectomy between April 2015 and July 2023, were analyzed. A total of 375 lymph nodes (180 metastatic, 195 benign) were evaluated. Two radiologists recorded morphological criteria (adipose hilum status, cortical appearance, extranodal extension, and short-axis diameter) and placed regions of interest to measure dual-energy parameters: attenuation at 40 and 70 keV, iodine concentration, water concentration and spectral slope. Normalized iodine concentration was calculated using the aorta as reference. Univariate analysis identified variables associated with metastasis. Multivariate logistic regression with cross-validation was used to construct two models: one based solely on morphological features and one integrating water concentration. Results: On univariate testing, all DECT parameters and morphological criteria differed significantly between metastatic and benign nodes (p < 0.01). In multivariate analysis, water concentration emerged as the only independent DECT predictor (odds ratio = 0.97; p = 0.002) alongside cortical abnormality, absence of adipose hilum, extranodal extension and short-axis diameter. The morphologic model achieved an area under the receiver operating characteristic curve (AUC) of 0.871. Increasing water concentration increased the AUC to 0.883 (ΔAUC = 0.012; p = 0.63, not significant), with internal cross-validation confirming stable performance. Conclusions: A model combining standard morphologic criteria with water concentration quantification on DECT accurately differentiates metastatic from benign axillary nodes in BC patients. Although iodine-based metrics remain valuable indicators of perfusion, water concentration offers additional tissue composition information. Future multicenter prospective studies with standardized imaging protocols are warranted to refine parameter thresholds and validate this approach for routine clinical use.
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(This article belongs to the Special Issue Enhancing Precision in Cancer Treatment: AI-Driven Innovations in Imaging)
Open AccessArticle
Spanish Paediatric Haematology and Oncology Survival Results and Trends, 1999–2022
by
Pau Alfonso-Comos, Álvaro Briz-Redón, José Luis Dapena Díaz, Susana Rives, José María Fernández Navarro, Jaime Verdú-Amorós, Adela Cañete and RETI-SEHOP Survival Working Group
Cancers 2026, 18(3), 362; https://doi.org/10.3390/cancers18030362 - 23 Jan 2026
Abstract
Background: Childhood cancer is the leading cause of natural death among children in high-income countries, despite treatment improvements. The Spanish Registry of Childhood Tumours (RETI-SEHOP) systematically records all cases treated within the network of SEHOP units. Using RETI-SEHOP data, we evaluated survival
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Background: Childhood cancer is the leading cause of natural death among children in high-income countries, despite treatment improvements. The Spanish Registry of Childhood Tumours (RETI-SEHOP) systematically records all cases treated within the network of SEHOP units. Using RETI-SEHOP data, we evaluated survival trends to assess progress in patient care, both overall and by tumour. Methods: A total of 20,534 childhood cancer cases (0–14 years) were recorded across the period 1999–2021. The 1-, 3-, and 5-year overall survival (OS) were estimated using the Kaplan–Meier method, applying the cohort approach for 1999–2018 and the period approach for 2019–2022. OS by age and sex was analysed in the recent 2009–2018 incidence cohort. Age-adjusted OS time trends were examined using joinpoint Cox models for 1999–2022. Results: For all tumours combined, 5-year OS increased from 75.4% to 84.6% between 1999–2003 and 2019–2022. While positive trends were identified for all haematological malignancies examined, a more varied scenario was evident for solid tumours, as ependymomas improved fastest (1.51 points annually), and sarcomas, except for rhabdomyosarcoma, remained stagnant. Conclusions: Our results reflect a period characterised by a combination of new therapeutic developments, improved diagnostics, and more refined risk stratification, which has ultimately led to a reduction in disease-related mortality.
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(This article belongs to the Special Issue Recent Advances in Epidemiology of Childhood Cancer)
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Open AccessReview
A Decade of Innovation in Breast Cancer (2015–2025): A Comprehensive Review of Clinical Trials, Targeted Therapies and Molecular Perspectives
by
Klaudia Dynarowicz, Dorota Bartusik-Aebisher, Sara Czech, Aleksandra Kawczyk-Krupka and David Aebisher
Cancers 2026, 18(3), 361; https://doi.org/10.3390/cancers18030361 - 23 Jan 2026
Abstract
The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as
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The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead.
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(This article belongs to the Section Cancer Therapy)
Open AccessCorrection
Correction: Jugel et al. Targeted Transposition of Minicircle DNA Using Single-Chain Antibody Conjugated Cyclodextrin-Modified Poly (Propylene Imine) Nanocarriers. Cancers 2022, 14, 1925
by
Willi Jugel, Stefanie Tietze, Jennifer Daeg, Dietmar Appelhans, Felix Broghammer, Achim Aigner, Michael Karimov, Gabriele Schackert and Achim Temme
Cancers 2026, 18(3), 360; https://doi.org/10.3390/cancers18030360 - 23 Jan 2026
Abstract
In the original publication [...]
Full article
(This article belongs to the Special Issue Cancer Smart Nanomedicine)
Open AccessReview
TREM2 in Urological Malignancies and Benign Lesions: Mechanistic Convergence, Functional Heterogeneity, and Translational Perspectives: A Narrative Review
by
Yu Dai, Yaqiang Feng, Cheng Wang, Helin Zhang and Panfeng Shang
Cancers 2026, 18(3), 359; https://doi.org/10.3390/cancers18030359 - 23 Jan 2026
Abstract
Triggering receptor expressed on myeloid cells-2 (TREM2) is a key myeloid immune checkpoint for macrophage plasticity. However, its functional landscape in urology is still incomplete. This review addresses this gap by providing the first systematic synthesis of TREM2 in urological malignancies (bladder, prostate,
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Triggering receptor expressed on myeloid cells-2 (TREM2) is a key myeloid immune checkpoint for macrophage plasticity. However, its functional landscape in urology is still incomplete. This review addresses this gap by providing the first systematic synthesis of TREM2 in urological malignancies (bladder, prostate, and renal cell carcinomas) and benign conditions. We find a strong correlation between TREM2 upregulation and adverse clinical outcomes in these cancers. Importantly, we highlight the phenomenon of “mechanistic convergence”: unlike the high context-dependency of other organ systems, TREM2 appears to drive progression in urological malignancies by a common convergent signaling hub, the PI3K/AKT pathway. This contrasts sharply with its metabolic role in benign prostatic hyperplasia and its protective role in non-malignant renal injury. We also consider the translational potential of TREM2 as a prognostic biomarker (specifically urine detection) and as a therapeutic target to reverse immunotherapy resistance.
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(This article belongs to the Section Cancer Pathophysiology)
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Open AccessArticle
Neoadjuvant Pembrolizumab Associated with Chemotherapy in Early Triple-Negative Breast Cancer Patients: Real-World Data from a French Single-Center Experience
by
Ichrak Ben Abdallah, Severine Guiu, Xavier Quantin, William Jacot and Philine Witkowski
Cancers 2026, 18(3), 358; https://doi.org/10.3390/cancers18030358 - 23 Jan 2026
Abstract
Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data
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Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data on treatment feasibility, efficacy, and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods: We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0). Results: We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2% of patients. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 29.3% of patients in the study population. The pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and the pCR rate (p = 0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p = 0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusions: The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial, with no treatment-related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates.
Full article
(This article belongs to the Special Issue Immune-Related Adverse Events in Cancer Immunotherapy)
Open AccessArticle
Autophagy-Related Proteins’ Immunohistochemical Expression and Their Potential Role as Biomarkers in Thymic Epithelial Tumors
by
Christina Yfanti, Georgia Levidou, Vicky Lampropoulou, Stefania Kokkali, Georgios Mandrakis, Stavros P. Papadakos, Dimitra Rontogianni and Stamatios Theocharis
Cancers 2026, 18(3), 357; https://doi.org/10.3390/cancers18030357 - 23 Jan 2026
Abstract
Background: Autophagy, a self-destructive cellular mechanism with a paradoxical nature, plays a part in both tumor suppression and induction by providing cancer cells with metabolic substrates, resulting in cell proliferation and survival. In this study, we aim to investigate the clinical significance of
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Background: Autophagy, a self-destructive cellular mechanism with a paradoxical nature, plays a part in both tumor suppression and induction by providing cancer cells with metabolic substrates, resulting in cell proliferation and survival. In this study, we aim to investigate the clinical significance of four autophagy pathway components (BECLIN, p62/, LC3b, ATG3) in pathogenetic mechanisms of thymic epithelial tumors (TETs) with possible prognostic importance. Methods: Immunohistochemistry was used to evaluate the cytoplasmic expression of BECLIN, p62, LC3b, and ATG3 in tumor cells of 99 TETs, and possible correlations with clinicopathological parameters were examined. Results: Higher BECLIN and p62 expression was associated with male gender (p = 0.027 and p = 0.014, respectively). B3 thymomas and thymic carcinomas (TCs) displayed higher p62 expression (p = 0.019), while LC3b expression was marginally higher in non-B3/TC TETs (p = 0.098). A positive correlation between higher BECLIN expression and advanced Masaoka–Koga stage was also observed (p = 0.009). ATG3 was not associated with any of the investigated clinicopathological parameters (p > 0.05). There was also no significant correlation between any of the four examined molecules and overall survival or relapse. Conclusions: Our findings indicate autophagy activation in B3/TC and advanced Masaoka–Koga stage cases. Further studies are needed to explore the role of these autophagy related proteins as potential biomarkers and therapeutic targets in TETs.
Full article
(This article belongs to the Special Issue New Insights into Thymic Tumors)
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The Influence of Molecular Factors on the Effectiveness of New Therapies in Endometrial Cancer—Latest Evidence and Clinical Trials
by
Wiktoria Mytych, Edyta Barnaś, Dorota Bartusik-Aebisher and David Aebisher
Cancers 2026, 18(3), 356; https://doi.org/10.3390/cancers18030356 - 23 Jan 2026
Abstract
Endometrial cancer (EC) is the most common gynecological cancer in developed countries, with approximately 417,000 new cases reported worldwide in 2020. Its incidence has been rising for the past 30 years, primarily due to population aging, obesity, and type 2 diabetes; obesity accounts
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Endometrial cancer (EC) is the most common gynecological cancer in developed countries, with approximately 417,000 new cases reported worldwide in 2020. Its incidence has been rising for the past 30 years, primarily due to population aging, obesity, and type 2 diabetes; obesity accounts for almost half of cases due to excessive estrogen production. The classic division into types I and II was replaced in 2013 by the molecular TCGA classification, which distinguishes four subtypes: POLE-ultramutated (best prognosis), MSI-hypermutated, copy-number low, and copy-number high (worst prognosis). This classification (refined in ProMisE and TransPORTEC) enables precise treatment: immunotherapy (pembrolizumab, dostarlimab) works excellently in dMMR/MSI-H tumors, PI3K/AKT/mTOR inhibitors and trastuzumab deruxtecan in selected molecular subtypes, and hormone therapy in ER-positive tumors. ctDNA monitoring supports therapeutic decisions. Integrating the molecular profile with FIGO allows for truly personalized treatment, although MMRp/MSS tumors remain a challenge. The future lies in multi-omics, new biomarkers, and combination therapies.
Full article
(This article belongs to the Special Issue What’s Behind the Scenes? New Insights in Endometrial Cancer Management and Risk Stratification (2nd Edition))
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