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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 Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 19.1 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 18 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
- Journal Clusters of Oncology: Cancers, Current Oncology, Onco and Targets.
Impact Factor:
4.4 (2024);
5-Year Impact Factor:
4.8 (2024)
Latest Articles
Radioligand Therapy in Meningiomas: Today’s Evidence, Tomorrow’s Possibilities
Cancers 2026, 18(2), 297; https://doi.org/10.3390/cancers18020297 (registering DOI) - 18 Jan 2026
Abstract
Meningiomas are the most common primary intracranial tumors, showing highly heterogeneous behavior and clinical outcomes. While the majority are benign, about one in five meningiomas are classified as higher grade (WHO Grade II–III), characterized by a more aggressive, treatment-resistant pathology. Although surgical resection
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Meningiomas are the most common primary intracranial tumors, showing highly heterogeneous behavior and clinical outcomes. While the majority are benign, about one in five meningiomas are classified as higher grade (WHO Grade II–III), characterized by a more aggressive, treatment-resistant pathology. Although surgical resection remains the first-line therapy, peptide receptor radionuclide therapy is emerging as a novel and promising option for advanced, multifocal, or recurrent disease. The theranostic paradigm allows simultaneous detection and treatment of somatostatin receptor-expressing lesions using a single radiopharmaceutical. In this review, we explore the evolving role of PRRT in the management of meningiomas. We provide an integrated overview of preclinical findings—including radiosensitization mechanisms—and summarize the rapidly expanding clinical literature, which in recent years has grown both in patient numbers and in methodological sophistication. Particular emphasis is placed on advances in dosimetry, quantitative imaging, and radiomics, which are beginning to refine patient selection and improve response prediction. Together, current evidence highlights the therapeutic potential of radionuclide therapy in aggressive or refractory meningiomas and underscores the need for further prospective trials to define its optimal clinical application.
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(This article belongs to the Special Issue Feature Review for Cancer Therapy: 2nd Edition)
Open AccessSystematic Review
Technology-Enabled (P)rehabilitation for Patients Undergoing Cancer Surgery: A Systematic Review and Meta-Analysis
by
Tiffany R. Tsoukalas, Zirong Bai, Claire Jeon, Roy Huynh, Eva Gu, Kate Alexander, Paula R. Beckenkamp, Adrian Boscolo, Kilian Brown, Phyllis Butow, Sharon Carey, Fang Chen, Meredith Cummins, Haryana M. Dhillon, Vesna Dragoje, Kailey Gorman, Matthew Halpin, Abby Haynes, Ilona Juraskova, Sascha Karunaratne, Jamie Keck, Bora Kim, Cherry Koh, Qiang Li, Lara Lipton, Xiaoqiu Liu, Jaime Macedo, Rebecca Mercieca-Bebber, Renee Moreton, Rachael L. Morton, Julie Redfern, Bernhard Riedel, Angus Ritchie, Charbel Sandroussi, Cathy Slattery, Allan Ben Smith, Michael Solomon, Flora Tao, Kate White, Kate Wilson, Kahlia Wolsley, Kun Yu and Daniel Steffensadd
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Cancers 2026, 18(2), 296; https://doi.org/10.3390/cancers18020296 (registering DOI) - 18 Jan 2026
Abstract
Background/Objectives: (P)rehabilitation, comprising structured exercise, nutritional optimisation, and/or psychological support delivered pre- or postoperatively, has demonstrated efficacy in improving outcomes across the cancer care continuum. However, access remains limited. Technology-enabled (p)rehabilitation offers a novel solution with the potential to enhance equity and continuity
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Background/Objectives: (P)rehabilitation, comprising structured exercise, nutritional optimisation, and/or psychological support delivered pre- or postoperatively, has demonstrated efficacy in improving outcomes across the cancer care continuum. However, access remains limited. Technology-enabled (p)rehabilitation offers a novel solution with the potential to enhance equity and continuity of care. This systematic review aimed to evaluate the efficacy of technology-enabled (p)rehabilitation on perioperative and patient-reported outcomes among individuals undergoing thoracic and/or abdominopelvic cancer surgery. Methods: Six databases were search from inception to October 2024. Eligible studies were randomised controlled trials (RCTs) comparing technology-enabled (p)rehabilitation with usual care, placebo, or non-technology-based interventions in adults undergoing thoracic and/or abdominopelvic cancer surgery. Outcomes included postoperative complications, hospital readmissions, hospital length of stay (LOS), quality of life (QoL), pain, anxiety, depression, fatigue, distress, and satisfaction. Higher scores indicated improved QoL or worse symptom severity. Risk of bias was assessed using the revised Cochrane tool, and evidence strength was determined using GRADE methodology. Relative risks (RR) and mean differences (MD) were calculated using random-effects meta-analysis. Results: Seventeen RCTs (18 publications, n = 1690) were included. Trials most commonly evaluated application-based platforms (n = 8) and the majority exhibited some risk of bias. Technology-enabled (p)rehabilitation was associated with a significant reduction in LOS (MD = 1.33 days; 95% CI: 0.59–2.07; seven trials), and improvements in pain (MD = 6.12; 95% CI: 3.40–8.84; four trials), depression (MD = 2.82; 95% CI: 0.65–4.99; five trials), fatigue (MD = 10.10; 95% CI: 6.97–13.23; three trials) and distress (MD = 1.23; 95% CI: 0.30–2.16; single trial) compared with controls. Conclusions: Technology-enabled (p)rehabilitation shows promise in reducing LOS and improving selected patient-reported outcomes following thoracic and abdominopelvic cancer surgery. Although evidence is limited due to the small number of studies, modest sample sizes, methodological heterogeneity, and intervention variability, the overall findings justify further investigation. Large-scale, adequately powered clinical trials are required to confirm efficacy and guide clinical effectiveness and implementation studies.
Full article
(This article belongs to the Special Issue Preoperative Optimisation in Patients Undergoing Cancer Surgery: 2nd Edition)
Open AccessArticle
The Effect of Smoking and Pre-Allogeneic Hematopoietic Cell Transplant Pulmonary Comorbidity on the Incidence of Lung Graft-Versus-Host Disease and Post-Transplant Outcomes
by
Ebaa Reda, Mohammed Kawari, Mariana Pinto Pereira, Mats Remberger, Ambrose Lau, Arjun D. Law, Rajat Kumar, Igor Novitzky-Basso, Wilson Lam, Ivan Pasic, Armin Gerbitz, Auro Viswabandya, Dennis D. Kim, Jeffrey H. Lipton, Jonas Mattsson and Fotios V. Michelis
Cancers 2026, 18(2), 295; https://doi.org/10.3390/cancers18020295 (registering DOI) - 18 Jan 2026
Abstract
Background/Objectives: Smoking is linked to an increased risk of pulmonary complications and adverse outcomes following allogeneic hematopoietic cell transplantation (Allo-HCT). Unfortunately, data is rarely correlated with the incidence of GVHD and does not show whether smoking has a negative impact independent from underlying
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Background/Objectives: Smoking is linked to an increased risk of pulmonary complications and adverse outcomes following allogeneic hematopoietic cell transplantation (Allo-HCT). Unfortunately, data is rarely correlated with the incidence of GVHD and does not show whether smoking has a negative impact independent from underlying pulmonary comorbidities. Methods: We retrospectively analyzed 407 patients who underwent Allo-HCT between January 2019 and May 2021 and evaluated the impact of smoking history and pre-transplant pulmonary comorbidities on the risk of outcomes including graft-versus-host disease (GVHD), overall survival (OS), and non-relapse mortality (NRM). Results: Patients were divided into the following groups: Group A: smokers with pre-transplant pulmonary comorbidity, 40 pts (9.8%); Group B: non-smokers with pre-transplant pulmonary comorbidity, 71 pts (17.4%); Group C: smokers without pre-transplant pulmonary comorbidity, 105 pts (25.8%); and Group D: non-smokers without pre-transplant pulmonary comorbidity, 191 pts (46.9%). Smokers were also grouped by their smoking history (<10 pack-years (59 pts), 11 to 25 pack-years (50 pts), and >25 pack-years (35 pts)) and by smoking recency: Recent (until Allo-HCT), Former (quit > 1 year ago), and Remote smokers (quit > 10 years ago). Our results showed that Group A demonstrated increased chronic lung GVHD compared to the other groups (p = 0.01). The 3-year OS was lowest in Group A at 45.0%, compared to 70.4%, 62.4%, and 69.4% (p = 0.006), and the NRM was highest at 37.5%, compared to 15.5%, 18.2%, and 14.7% in Groups B, C, and D, respectively (p = 0.001). Smoking recency and higher pack-year dose were associated with worse outcomes. Conclusions: Our study demonstrated the negative synergistic effect of smoking history and pre-transplant pulmonary comorbidities on the incidence of lung GVHD, OS, and NRM.
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(This article belongs to the Special Issue Current Use of Hematopoietic Cell Transplantation in Hematologic Malignancies)
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Open AccessArticle
Metabolic Crosstalk in Triple-Negative Breast Cancer Lung Metastasis: Differential Effects of Vitamin D and E in a Co-Culture System
by
Balquees Kanwal, Saranya Pounraj, Rumeza Hanif and Zaklina Kovacevic
Cancers 2026, 18(2), 294; https://doi.org/10.3390/cancers18020294 (registering DOI) - 18 Jan 2026
Abstract
Background: Triple-negative breast cancer (TNBC) is more likely to metastasise to the lungs than other breast cancer (BrCa) types, yet the molecular interactions within the tumour microenvironment (TME) at secondary sites remain poorly understood. Methods: This pilot study aimed to explore the metabolic
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Background: Triple-negative breast cancer (TNBC) is more likely to metastasise to the lungs than other breast cancer (BrCa) types, yet the molecular interactions within the tumour microenvironment (TME) at secondary sites remain poorly understood. Methods: This pilot study aimed to explore the metabolic crosstalk between MDA-MB-231 TNBC cells and MRC-5 lung fibroblasts within a co-culture system to replicate the lung metastatic TME. Co-cultures were also treated with Vitamin D or Vitamin E to evaluate the effects of these nutraceuticals on the metabolic crosstalk between TNBC cells and fibroblasts. Results: Our findings demonstrate that co-culture induced the activation of fibroblasts into cancer-associated fibroblasts (CAFs), evidenced by increased α-SMA and FAP expression. Metabolic profiling revealed that TNBC cells in co-culture displayed increased expression of enzymes associated with oxidative phosphorylation (OXPHOS) and glutamine metabolism, while fibroblasts exhibited a metabolic profile consistent with glycolysis and lactate metabolism. Vitamin D inhibited lactate metabolism and HIF-1α expression in fibroblasts while suppressing TCA cycle activity in cancer cells, suggesting a potential role in disrupting oncogenic metabolic crosstalk. Conversely, Vitamin E treatment was associated with increased expression of TCA cycle and oxidative metabolism-related markers in BrCa cells without significantly affecting fibroblast glycolysis. Such differential metabolic responses may contribute to metabolic heterogeneity within the tumour microenvironment. Conclusions: These results provide valuable insights into the metabolic dynamics of TNBC metastases in the lung TME and demonstrate that Vitamins D and E exert distinct effects on metabolic crosstalk between cancer cells and fibroblasts. These findings may have significant implications for the potential supplementation of Vitamins D and E in patients with metastatic TNBC and justify further in-depth analysis.
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(This article belongs to the Special Issue Tumor Microenvironment of Breast Cancer—2nd Edition)
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Open AccessArticle
Conversational AI-Enabled Precision Oncology Reveals Context-Dependent MAPK Pathway Alterations in Hispanic/Latino and Non-Hispanic White Colorectal Cancer Stratified by Age and FOLFOX Exposure
by
Fernando C. Diaz, Brigette Waldrup, Francisco G. Carranza, Sophia Manjarrez and Enrique Velazquez-Villarreal
Cancers 2026, 18(2), 293; https://doi.org/10.3390/cancers18020293 (registering DOI) - 17 Jan 2026
Abstract
Background: Colorectal cancer (CRC) demonstrates substantial clinical and biological diversity across age groups, ancestral backgrounds, and treatment settings, alongside a rising incidence of early-onset disease (EOCRC). The mitogen-activated protein kinase (MAPK) pathway is a major driver of CRC development and therapy response; however,
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Background: Colorectal cancer (CRC) demonstrates substantial clinical and biological diversity across age groups, ancestral backgrounds, and treatment settings, alongside a rising incidence of early-onset disease (EOCRC). The mitogen-activated protein kinase (MAPK) pathway is a major driver of CRC development and therapy response; however, the distribution and prognostic value of MAPK alterations across distinct patient subgroups remain unclear. Methods: We analyzed 2515 CRC tumors with harmonized demographic, clinical, genomic, and treatment metadata. Patients were stratified by ancestry (Hispanic/Latino [H/L] vs. non-Hispanic White [NHW]), age at diagnosis (early-onset [EO] vs. late-onset [LO]), and FOLFOX chemotherapy exposure. MAPK pathway alterations were identified using a curated gene set encompassing canonical EGFR-RAS-RAF-MEK-ERK signaling components and regulatory nodes. Conversational artificial intelligence (AI-HOPE and AI-HOPE-MAPK) enabled natural language-driven cohort construction and exploratory analytics; findings were validated using Fisher’s exact testing, chi-square analyses, and Kaplan–Meier survival estimates. Results: MAPK pathway disruption demonstrated marked heterogeneity across ancestry and treatment contexts. Among EO H/L patients, FGFR3, NF1, and RPS6KA6 mutations were significantly enriched in tumors not receiving FOLFOX, whereas PDGFRB alterations were more frequent in FOLFOX-treated EO H/L tumors relative to EO NHW counterparts. In late-onset H/L disease, NTRK2 and PDGFRB mutations were more common in non-FOLFOX tumors. Distinct MAPK-associated alterations were also observed among NHW patients, particularly in non-FOLFOX settings, including AKT3, FGF4, RRAS2, CRKL, DUSP4, JUN, MAPK1, RRAS, and SOS1. Survival analyses provided borderline evidence that MAPK alterations may be linked to improved overall survival in treated EO NHW patients. Conversational AI markedly accelerated analytic throughput and multi-parameter discovery. Conclusions: Although MAPK alterations are pervasive in CRC, their distribution varies meaningfully by ancestry, age, and treatment exposure. These findings highlight NF1, MAPK3, RPS6KA4, and PDGFRB as potential biomarkers in EOCRC and H/L patients, supporting the need for ancestry-aware precision oncology approaches.
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(This article belongs to the Special Issue Innovations in Addressing Disparities in Cancer)
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Open AccessArticle
The Impact of Endpoint Definitions on Predictors of Progression in Active Surveillance for Early Prostate Cancer
by
Kieran Sandhu, Artitaya Lophatananon and Vincent J. Gnanapragasam
Cancers 2026, 18(2), 292; https://doi.org/10.3390/cancers18020292 (registering DOI) - 17 Jan 2026
Abstract
Background/Objectives: There is conflicting data on which factors predict progression events in active surveillance for early prostate cancer. Here, we explored the value of different clinicopathological variables and whether progression endpoint definitions impact predictive utility. Methods: Clinicopathological variables were extracted from
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Background/Objectives: There is conflicting data on which factors predict progression events in active surveillance for early prostate cancer. Here, we explored the value of different clinicopathological variables and whether progression endpoint definitions impact predictive utility. Methods: Clinicopathological variables were extracted from the STRATified CANcer Surveillance (STRATCANs) prospective AS database and included biopsy features (core positivity, cancer core length, and percentage core involvement) and MRI features (Likert score, lesion size, and location), as well as baseline PSA density [PSAd] and Cambridge Prognostic Group (CPG). These were tested against AS endpoint definitions of (1) progression to ≥CPG3, (2) any pathological progression and two definitions from the literature, (3) ≥GG3 or change to treatment, and (4) ≥GG4, metastasis or cancer-related mortality. Predictors were assessed using regression analysis. Results: Data from 296 men were included (median age, 66; follow-up, 5 years). Progression per definition (1–4) occurred in 46 (15.5%), 54 (18.2%), 84 (28.4%), and 10 (3.4%) men. In univariate analysis using Definition 1, no biopsy parameter was independently predictive of progression, while the MRI Likert score (p = 0.02) was the only significant imaging parameter. For Definition 2, core positivity (p = 0.003) and MRI Likert score (p = 0.01) were significant predictors in univariate analyses, while for Definition 3, tumour core length (p = 0.005), core positivity (p = 0.002), and MRI Likert score (p = 0.003) were all predictive in univariate analyses. In multivariate analysis, however, the only consistent independent predictor was PSAd, regardless of endpoint definition. No variables predicted Definition 4 progression. Conclusions: AS endpoint selection appears to define which variables predict progression. Using progression to ≥CPG 3 as an unambiguous AS endpoint, neither biopsy nor MRI variables added incremental value in predicting progression. PSAd, however, appears to be a robust and independent generalisable progression predictor.
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(This article belongs to the Section Cancer Epidemiology and Prevention)
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Open AccessArticle
MRI-Based Delta Necrosis as a Prognostic Marker Following Neoadjuvant Chemotherapy in Soft Tissue Sarcoma
by
Harold Bravo Thompson, Priya Chattopadhyay, Ty Subhawong, Malcolm-Christopher Palmer, Sergio Torralbas Fitz, Brooke Crawford, Andrew Rosenberg, H. Thomas Temple and Emily Jonczak
Cancers 2026, 18(2), 291; https://doi.org/10.3390/cancers18020291 (registering DOI) - 17 Jan 2026
Abstract
Background: The prognostic value of treatment-induced necrosis in soft STS remains uncertain. This study evaluated whether MRI-based changes in necrosis (Δ necrosis) between pre- and post-neoadjuvant chemotherapy scans correlate with pathologic necrosis and clinical outcomes. Methods: In this retrospective cohort, 27 patients with
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Background: The prognostic value of treatment-induced necrosis in soft STS remains uncertain. This study evaluated whether MRI-based changes in necrosis (Δ necrosis) between pre- and post-neoadjuvant chemotherapy scans correlate with pathologic necrosis and clinical outcomes. Methods: In this retrospective cohort, 27 patients with STS who received neoadjuvant chemotherapy and underwent pre- and post-treatment MRI were analyzed. Necrosis was graded categorically (<5%, 5–25%, 25–50%, 50–75%, 75–95%, and >95%), and Δ necrosis was calculated as the change in estimated necrosis between scans. Correlations between MRI-derived and pathologic necrosis were assessed using Spearman’s rank coefficient. Survival analyses (progression-free, local recurrence-free, and disease-specific overall survival) were performed using Kaplan–Meier and log-rank tests. Results: Post-treatment MRI necrosis moderately correlated with pathologic necrosis (ρ = 0.44, p = 0.028), whereas Δ necrosis showed a weaker, nonsignificant correlation (ρ = 0.24, p = 0.24). Neither MRI-based nor pathologic necrosis thresholds were associated with survival outcomes. Conclusions: MRI-based Δ necrosis did not predict pathologic necrosis or oncologic outcomes in STS, suggesting that radiologic changes in necrosis may not serve as reliable markers of therapeutic response. Future studies integrating quantitative imaging and standardized pathology protocols together with future exploration of molecular tools such as ctDNA are needed to refine treatment assessment in STS.
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(This article belongs to the Special Issue Innovative Strategies and Techniques in Diagnosing, Treating and Surveying Soft Tissue Sarcomas)
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Open AccessArticle
Epidemiology of Primary Urethral Cancer: Insights from Four European Countries with a Focus on Poland
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Iwona Wnętrzak, Urszula Wojciechowska, Joanna A. Didkowska, Jakub Dobruch, Mateusz Czajkowski and Roman Sosnowski
Cancers 2026, 18(2), 290; https://doi.org/10.3390/cancers18020290 (registering DOI) - 17 Jan 2026
Abstract
Background/Purpose: Primary urethral cancer is a rare malignancy, accounting for less than 1% of all urogenital cancers. Current epidemiological data from Europe are scarce and outdated. Therefore, the analyzes and comparison of the incidence and mortality of PUC in selected European countries,
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Background/Purpose: Primary urethral cancer is a rare malignancy, accounting for less than 1% of all urogenital cancers. Current epidemiological data from Europe are scarce and outdated. Therefore, the analyzes and comparison of the incidence and mortality of PUC in selected European countries, with particular focus on Poland, based on the most recent available registry data, were performed. Methods: Our study is based on country-level data and is descriptive in nature. Incidence data for PUC were obtained from the national cancer registries of Poland, Latvia, Slovenia, and Hungary. Mortality data were sourced from the WHO Mortality Database. Age-standardized incidence rates were calculated for two time intervals (2000–2009 and 2010–2019). Age-standardized mortality rates for individuals aged ≥45 years were calculated using the European Standard Population (ESP2013). Trends in incidence and mortality in Poland were analyzed using a five-year moving average. Results: The highest incidence of PUC was observed in Hungary, while Poland showed the lowest incidence. Latvia had the highest ASMRs for both sexes, whereas Poland and Greece reported the lowest mortality rates. Despite slight annual fluctuations, the overall PUC mortality rate in Poland has remained stable. Our study is limited by the relatively short analyzed period (2000–2021), restricted availability of C68.0 incidence data from national cancer registries, and incomplete mortality data in the WHO mortality database. Conclusions: This first contemporary comparative analysis of PUC epidemiology in Europe highlights the rarity of this malignancy and the limited data availability. Based on the knowledge drawn from the literature presented in the article on the impact of centralization on the increase in overall survival and the decrease in mortality in rare cancers, the authors believe that centralization of care can improve PUC patient outcomes.
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(This article belongs to the Special Issue Urological Cancer: Epidemiology and Genetics)
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Open AccessSystematic Review
MRI-Based Prediction of Vestibular Schwannoma: Systematic Review
by
Cheng Yang, Daniel Alvarado, Pawan Kishore Ravindran, Max E. Keizer, Koos Hovinga, Martinus P. G. Broen, Henricus P. M. Kunst and Yasin Temel
Cancers 2026, 18(2), 289; https://doi.org/10.3390/cancers18020289 (registering DOI) - 17 Jan 2026
Abstract
Background: The vestibular schwannoma (VS) is the most common cerebellopontine angle tumor in adults, exhibiting a highly variable natural history, from stability to rapid growth. Accurate, the non-invasive prediction of tumor behavior is essential to guide personalized management and avoid overtreatment or
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Background: The vestibular schwannoma (VS) is the most common cerebellopontine angle tumor in adults, exhibiting a highly variable natural history, from stability to rapid growth. Accurate, the non-invasive prediction of tumor behavior is essential to guide personalized management and avoid overtreatment or delayed intervention. Objective: To systematically review and synthesize the evidence on MRI-based biomarkers for predicting VS growth and treatment responses. Methods: We conducted a PRISMA-compliant search of PubMed, EMBASE, and Cochrane databases for studies published between 1 January 2000 and 1 January 2025, addressing MRI predictors of VS growth. Cohort studies evaluating texture features, signal intensity ratios, perfusion parameters, and apparent diffusion coefficient (ADC) metrics were included. Study quality was assessed using the NOS (Newcastle–Ottawa Scale) score, GRADE (Grading of Recommendations, Assessment, Development and Evaluation), and ROBIS (Risk of Bias in Systematic reviews) tool. Data on diagnostic performance, including the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and p value, were extracted and descriptively analyzed. Results: Ten cohort studies (five retrospective, five prospective, total n = 525 patients) met the inclusion criteria. Texture analysis metrics, such as kurtosis and gray-level co-occurrence matrix (GLCM) features, yielded AUCs of 0.65–0.99 for predicting volumetric or linear growth thresholds. Signal intensity ratios on gadolinium-enhanced T1-weighted images for tumor/temporalis muscle achieved a 100% sensitivity and 93.75% specificity. Perfusion MRI parameters (Ktrans, ve, ASL, and DSC derived blood-flow metrics) differentiated growing from stable tumors with AUCs up to 0.85. ADC changes post-gamma knife surgery predicted a favorable response, though the baseline ADC had limited value for natural growth prediction. The heterogeneity in growth definitions, MRI protocols, and retrospective designs remains a key limitation. Conclusions: MRI-based biomarkers may provide exploratory signals associated with VS growth and treatment responses. However, substantial heterogeneity in growth definitions and MRI protocols, small single-center cohorts, and the absence of external validation currently limit clinical implementation.
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(This article belongs to the Special Issue The Development and Application of Imaging Biomarkers in Cancer)
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Open AccessReview
Matrix Metalloproteinases in Hepatocellular Carcinoma: Mechanistic Roles and Emerging Inhibitory Strategies for Therapeutic Intervention
by
Alexandra M. Dimesa, Mathew A. Coban and Alireza Shoari
Cancers 2026, 18(2), 288; https://doi.org/10.3390/cancers18020288 (registering DOI) - 17 Jan 2026
Abstract
Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes
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Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases.
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(This article belongs to the Section Cancer Drug Development)
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Photothermal Therapy-Induced Immunogenic Cell Death Synergistically Enhances the Therapeutic Effect of Immune Checkpoint Inhibitors
by
Shogo Yasuda, Yui Horikawa, Mei Ohashi, Mai Amou, Taisei Kanamori, Duan Runjing, Yuta Tamemoto, Wei Xu, Takuro Niidome, Akihiro Hisaka and Hiroto Hatakeyama
Cancers 2026, 18(2), 287; https://doi.org/10.3390/cancers18020287 - 16 Jan 2026
Abstract
Background/Objectives: To improve the response rate of immune checkpoint inhibitors (ICIs), inducing immunogenic cell death (ICD) is a promising approach. Photothermal therapy (PTT) induces immunogenic cell death and activates anti-tumor immunity. While there are various ICD inducers, the difference in ICD induction by
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Background/Objectives: To improve the response rate of immune checkpoint inhibitors (ICIs), inducing immunogenic cell death (ICD) is a promising approach. Photothermal therapy (PTT) induces immunogenic cell death and activates anti-tumor immunity. While there are various ICD inducers, the difference in ICD induction by various modalities is poorly understood. In this study, we found previously unrecognized advantages of PTT compared to anti-cancer drugs and showed the usefulness of PTT as an anti-cancer drug-free approach to be combined with immunotherapy. Methods: Gold nanorods were synthesized as photothermal agents and added to culture medium or locally administered to tumor tissues. Mitoxantrone (MIT), an ICD inducer, and cisplatin (CDDP), a non-ICD inducer, were compared with PTT. To assess the induction of ICD, the subcellular localization and amounts of high mobility group box 1 (HMGB1) and calreticulin (CRT) were observed using immunofluorescent staining. FM3A tumor-bearing mice were treated with PTT or anti-cancer drugs, and cell death and DAMPs localization in tumor tissues were analyzed. Also, the supra-additive effect of PTT on ICI was observed. Tumor-infiltrating CD8+ T cells were examined to evaluate the immune status in tumor tissues. Results: In vivo assays showed that PTT induces HMGB1 release and increased expression of CRT on the cell membrane. Moreover, PTT showed a supra-additive effect in terms of therapeutic effect and anti-tumor activation when combined with an immune checkpoint inhibitor. Conclusions: In this study, we demonstrated that PTT induced ICD-related signaling and improved the response rate of ICI, which means PTT is a promising combination therapy with ICI.
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(This article belongs to the Section Cancer Immunology and Immunotherapy)
Open AccessReview
Prehabilitation in Adult Cancer Patients Undergoing Chemotherapy or Radiotherapy: A Scoping Review
by
Dylan Kwan, Wesley Kwan, Anchal Badwal, Tuti Puol, Justin Zou Deng, Raymond Wang, Saad Ahmed, Alexandria Mansfield, Rouhi Fazelzad and Jennifer Jones
Cancers 2026, 18(2), 286; https://doi.org/10.3390/cancers18020286 - 16 Jan 2026
Abstract
Purpose: The effectiveness and feasibility of cancer prehabilitation have been well-validated in surgical settings, but its role in non-surgical treatments, such as chemotherapy and radiotherapy (RT), remains unclear. This scoping review aims to systematically explore the existing literature on prehabilitation programs for
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Purpose: The effectiveness and feasibility of cancer prehabilitation have been well-validated in surgical settings, but its role in non-surgical treatments, such as chemotherapy and radiotherapy (RT), remains unclear. This scoping review aims to systematically explore the existing literature on prehabilitation programs for non-surgical cancer treatments. Methods: Following the scoping review methodology developed by the Joanna Briggs Institute, seven databases were systematically searched from their inception to October 2024 for peer-reviewed studies involving prehabilitation prior to non-surgical treatment. Data were extracted and reported adhering to PRISMA-ScR guidelines, using a convergent synthesis design to present qualitative and quantitative evidence. No formal risk-of-bias or quality appraisal was conducted. Results: Of 22,122 studies, 39 met the inclusion criteria, yielding a combined sample of 6073 patients and thirty-four unique interventions. Sample sizes ranged from 9 to 1992, with randomized control trials being the most common (16). Head and neck cancer was the most frequently studied, followed by breast, esophageal/gastric, and lung cancer. Of the included interventions, 23 were unimodal and 16 were multimodal. Exercise was the most common component (30), with nutrition (13), psychosocial (10), and educational (8) components also present. Most efficacy studies (84%) reported improved outcomes and nearly all (93%) feasibility studies found prehabilitation acceptable and implementable. Conclusions: This review highlights a growing body of literature examining prehabilitation prior to chemotherapy or RT in adult cancer patients, with studies suggesting potential benefits and feasibility. However, long-term trials, especially in diverse cancers and older populations, remain scarce. Our results provide insight into future implementation, evaluation of outcomes, and directions for future prehabilitation research.
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(This article belongs to the Special Issue Beyond Cancer: Enhancing Quality of Life for Cancer Survivors (Second Edition))
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Liquid Biopsy in Clear Cell Renal Cell Carcinoma: Diagnostic Potential of Urinary miRNAs
by
Giacomo Vannuccini, Alessio Paladini, Matteo Mearini, Francesca Cocci, Giuseppe Giardino, Paolo Mangione, Vincenza Maulà, Daniele Mirra, Ettore Mearini and Giovanni Cochetti
Cancers 2026, 18(2), 285; https://doi.org/10.3390/cancers18020285 - 16 Jan 2026
Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs
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Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring.
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(This article belongs to the Special Issue miRNAs in Targeted Cancer Therapy)
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Phase I Study of Mogamulizumab in Combination with Pembrolizumab in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma—A National Cancer Institute Experimental Therapeutics Clinical Trials Network (NCI-ETCTN) Trial
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Erel Joffe, Anita Kumar, Joseph M. Tuscano, Alison J. Moskowitz, Colette Owens, Ariela Noy, Maria Lia Palomba, Andrew D. Zelenetz, Andy Ni, Elad Sharon and Santosha Vardhana
Cancers 2026, 18(2), 284; https://doi.org/10.3390/cancers18020284 - 16 Jan 2026
Abstract
Introduction: Immune evasion through inhibition of effector T cells is a key survival mechanism of lymphoma cells. We hypothesized that reinstating effector T cell activity through concurrent inhibition of the PD1/PD-L1 axis and of Treg activity will result in a synergistic anti-tumor
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Introduction: Immune evasion through inhibition of effector T cells is a key survival mechanism of lymphoma cells. We hypothesized that reinstating effector T cell activity through concurrent inhibition of the PD1/PD-L1 axis and of Treg activity will result in a synergistic anti-tumor effect with an acceptable toxicity profile. Methods: Phase I multi-institutional NCI-ETCTN trial aimed to evaluate the safety and tolerability of the combination of mogamulizumab and pembrolizumab in relapsed or refractory non-Hodgkin lymphoma. The study used a 3 + 3 design. Treatment consisted of mogamulizumab 1 mg/kg on days 1, 8, and 15 of cycle 1, followed by 1.5 mg/kg on day 1 of each subsequent 21-day cycle in combination with pembrolizumab 200 mg on day 1 of each cycle. A de-escalation level was defined as a 50% reduction in the dose of mogamulizumab (registered in clinicaltrials.gov NCT03309878). Results: The study was discontinued early, after treating seven patients (two angioimmunoblastic T cell lymphoma, four transformed follicular lymphoma, and one diffuse large B cell lymphoma of germinal center subtype) for concerns of futility and non-tolerability. Only two patients completed the first two cycles of treatment. Three patients presented with an early progression and three withdrew consent in the setting of general deterioration with clinically suspected progression. All six patients expired shortly after withdrawal from the study. The remaining patient experienced stress cardiomyopathy during the third cycle and was taken off the study. Discussion: In striking difference to the observation in solid malignancies, the combination of mogamulizumab with pembrolizumab was associated with low tolerability and suspected hyper-progression in patients with lymphoma.
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(This article belongs to the Special Issue Clinical Trials for Diffuse Large B-Cell Lymphomas (DLBCL))
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Plasma Levels of Aromatase, Cathepsin S and Matrix Metalloproteinase 1 in Renal Cell Carcinomas: Implications for Tumor Progression and Diagnostic Value
by
Tomasz Guszcz, Anna Sankiewicz and Ewa Gorodkiewicz
Cancers 2026, 18(2), 283; https://doi.org/10.3390/cancers18020283 - 16 Jan 2026
Abstract
Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage
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Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL−1. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC.
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(This article belongs to the Section Cancer Biomarkers)
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Aberrant CD25 and Increased CD123 Expression Are Common in Acute Myeloid Leukemia with KMT2A Partial Tandem Duplication and Are Associated with FLT3 Internal Tandem Duplication
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Qing Wei, Guilin Tang, Shaoying Li, Sa A. Wang, Pei Lin, Wei Wang, Sanam Loghavi, Wei J. Wang, L. Jeffrey Medeiros and Jie Xu
Cancers 2026, 18(2), 282; https://doi.org/10.3390/cancers18020282 - 16 Jan 2026
Abstract
Background: KMT2A partial tandem duplication (PTD) occurs in approximately 5–10% of acute myeloid leukemia (AML) cases and is associated with poor prognosis. While its cytogenetic and molecular features are well described, the immunophenotypic characteristics of AML with KMT2A-PTD remain incompletely defined. Methods:
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Background: KMT2A partial tandem duplication (PTD) occurs in approximately 5–10% of acute myeloid leukemia (AML) cases and is associated with poor prognosis. While its cytogenetic and molecular features are well described, the immunophenotypic characteristics of AML with KMT2A-PTD remain incompletely defined. Methods: We identified 47 cases of AML with KMT2A-PTD by optical genome mapping. All cases underwent flow cytometric immunophenotypic analysis and next-generation sequencing using an 81-gene panel. Results: The cohort included 32 men and 15 women with a median age of 67 years (range, 19–87). Thirty-eight cases were de novo AML, and nine were secondary to myelodysplastic syndrome and/or myeloproliferative neoplasm. Most cases (93%) demonstrated a normal or non-complex karyotype. The most frequent mutations involved FLT3-ITD (47%), DNMT3A (43%), and RUNX1 (23%). Thirty-one cases (66%) were granulocytic, while 16 (34%) showed granulocytic and/or monocytic differentiation. Blasts uniformly expressed HLA-DR and frequently expressed CD117 (91%) and CD34 (79%). Increased expression of CD123 (74%) and CD117 (43%) and decreased expression of HLA-DR (74%) and CD38 (69%) were common. Aberrant CD25 expression was observed in 51% of cases. Increased CD123 and aberrant CD25 expression were significantly associated with FLT3-ITD mutations (both p < 0.0001) but not with other recurrent mutations. There was no correlation between FLT3-ITD mutation and expression levels of CD117, CD38 or HLA-DR (all p > 0.05). Conclusions: AML with KMT2A-PTD shows distinctive immunophenotypic features with increased CD123 and aberrant CD25 expression, both associated with FLT3-ITD. These markers may have diagnostic and therapeutic relevance in this AML subtype.
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(This article belongs to the Special Issue Advances in Pathology of Lymphoma and Leukemia)
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Detection of Breast Lesions Utilizing iBreast Exam: A Pilot Study Comparison with Clinical Breast Exam
by
Victoria L. Mango, Marta Sales, Claudia Ortiz, Jennifer Moreta, Jennifer Jimenez, Varadan Sevilimedu, T. Peter Kingham and Delia Keating
Cancers 2026, 18(2), 281; https://doi.org/10.3390/cancers18020281 - 16 Jan 2026
Abstract
Background/Objectives: The iBreast Exam (iBE) electronically palpates the breast to identify possible abnormalities. The purpose of this study was to assess iBE feasibility and compare it to Clinical Breast Exam (CBE) for breast lesion detection. Methods: Prospective evaluation of 300 asymptomatic
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Background/Objectives: The iBreast Exam (iBE) electronically palpates the breast to identify possible abnormalities. The purpose of this study was to assess iBE feasibility and compare it to Clinical Breast Exam (CBE) for breast lesion detection. Methods: Prospective evaluation of 300 asymptomatic women, ≥18 years old, with CBE, iBE, and mammography was performed. Sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of iBE and CBE for detecting suspicious breast lesions were calculated using breast imaging as the reference standard. For women with one year follow up, the sensitivity, specificity, PPV, and NPV for cancer detection were calculated. Results: 300 women (mean age 58.9 years) underwent CBE, iBE, and mammography. In 2/300 (0.7%), CBE was positive; in 1/300 (0.3%), iBE was positive; and in 24/300 (8%), screening mammograms were positive. Nine had suspicious imaging findings with biopsy (three malignant and six benign). Of three cancers, all visualized mammographically, CBE and iBE detected an ipsilateral breast abnormality in one woman and missed two cancers (<2 cm). Sensitivity, specificity, NPV, and PPV of iBE and CBE were similar, with no statistically significant difference in NPV or PPV for detection of suspicious breast findings or breast cancer (p > 0.05). Conclusions: Mammography detected all breast cancers in our cohort and remains the standard of care. iBE is feasible to perform. Our pilot data demonstrates iBE performed similarly to CBE by trained nurse practitioners. Given our small study population, further investigation is warranted into the potential use of iBE where trained healthcare practitioners are not readily available.
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(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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[18F]FDG PET/MRI in Endometrial Cancer: Prospective Evaluation of Preoperative Staging, Molecular Characterization and Prognostic Assessment
by
Carolina Bezzi, Gabriele Ironi, Tommaso Russo, Giorgio Candotti, Federico Fallanca, Carlotta Sabini, Ana Maria Samanes Gajate, Samuele Ghezzo, Alice Bergamini, Miriam Sant’Angelo, Luca Bocciolone, Giorgio Brembilla, Paola Scifo, GianLuca Taccagni, Onofrio Antonio Catalano, Giorgia Mangili, Massimo Candiani, Francesco De Cobelli, Arturo Chiti, Paola Mapelli and Maria Picchioadd
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Cancers 2026, 18(2), 280; https://doi.org/10.3390/cancers18020280 - 16 Jan 2026
Abstract
Background/Objectives: Early and accurate characterization of endometrial cancer (EC) is crucial for patient management, but current imaging modalities lack in diagnostic accuracy and ability to assess molecular profiles. The aim of this study is to evaluate hybrid [18F]FDG PET/MRI’s diagnostic accuracy
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Background/Objectives: Early and accurate characterization of endometrial cancer (EC) is crucial for patient management, but current imaging modalities lack in diagnostic accuracy and ability to assess molecular profiles. The aim of this study is to evaluate hybrid [18F]FDG PET/MRI’s diagnostic accuracy in EC staging and role in predicting tumor aggressiveness, molecular characterization, and recurrence. Methods: A prospective study (ClinicalTrials.gov, ID:NCT04212910) evaluating EC patients undergoing [18F]FDG PET/MRI before surgery (2018–2024). Histology, immunohistochemistry, and patients’ follow-up (mean FU time: 3.13y) were used as the reference standard. [18F]FDG PET/MRI, PET only, and MRI only were independently reviewed to assess the diagnostic accuracy (ACC), sensitivity (SN), specificity (SP), and positive/negative predictive value (PPV, NPV). Imaging parameters were extracted from [18F]FDG PET and pcT1w, T2w, DWI, and DCE MRI. Spearman’s correlations, Fisher’s exact test, ROC-AUC analysis, Kaplan–Meier survival curves, log-rank tests and Cox proportional hazards models were applied. Results: Eighty participants with primary EC (median age 63 ± 12 years) were enrolled, with 17% showing LN involvement. [18F]FDG PET/MRI provided ACC = 98.75%, SN = 98.75%, and PPV = 100% for primary tumor detection, and ACC = 92.41%, SN = 84.62%, SP = 93.94%, PPV = 73.33%, and NPV = 96.88% for LN detection. PET/MRI parameters predicted LN involvement (AUC = 79.49%), deep myometrial invasion (79.78%), lymphovascular space invasion (82.00%), p53abn (71.47%), MMRd (74.51%), relapse (82.00%), and postoperative administration of adjuvant therapy (79.64%). Patients with a tumor cranio-caudal diameter ≥ 43 mm and MTV ≥ 13.5 cm3 showed increased probabilities of recurrence (p < 0.001). Conclusions: [18F]FDG PET/MR showed exceptional accuracy in EC primary tumor and LN detection. Derived parameters demonstrated potential ability in defining features of aggressiveness, molecular alterations, and tumor recurrence.
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(This article belongs to the Special Issue Molecular Biology, Diagnosis and Management of Endometrial Cancer)
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Modulation of Cancer-Associated Fibroblasts via the miR-624-5p/FAP Axis Drives Progression and Metastasis in Non-Small Cell Lung Cancer
by
Yan Zhao, Shuman Zhen, Xiaoxu Li, Xiaolin Chen, Xue Zhang, Xinming Zhao and Lihua Liu
Cancers 2026, 18(2), 279; https://doi.org/10.3390/cancers18020279 - 16 Jan 2026
Abstract
Background: Cancer-associated fibroblasts (CAFs) are key mediators of metastatic progression in non-small cell lung cancer (NSCLC). Fibroblast activation protein (FAP) serves as the hallmark of CAF activation. However, the upstream regulation of FAP remains elusive, limiting stroma-targeted therapy development. Methods: 68Ga-FAP inhibitor
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Background: Cancer-associated fibroblasts (CAFs) are key mediators of metastatic progression in non-small cell lung cancer (NSCLC). Fibroblast activation protein (FAP) serves as the hallmark of CAF activation. However, the upstream regulation of FAP remains elusive, limiting stroma-targeted therapy development. Methods: 68Ga-FAP inhibitor (FAPI)-04 PET/CT imaging was performed on 61 NSCLC patients to evaluate the clinical significance of FAP. CAFs and normal fibroblasts (NFs) were isolated from patient tissues. Bioinformatic analysis and qRT-PCR were employed to screen and validate miRNAs. Functional assays (CCK-8, collagen contraction, wound healing, transwell co-culture) were utilized to investigate the role of miR-624-5p in regulating fibroblast activation and the effects on the metastatic potential of NSCLC cells. The targeting relationship between miR-624-5p and FAP was validated using FISH, dual-luciferase assay, and Western blotting. Results: 68Ga-FAPI-04 uptake was higher in advanced NSCLC (p < 0.001) and correlated with tumor size, lymph node metastases, and distant metastases (p < 0.05). Isolated primary CAFs significantly enhanced the migration and invasion of A549 and PC9 cells compared to NFs (p < 0.001). We identified miR-624-5p as a significantly downregulated miRNA in CAFs (p < 0.001). Functionally, miR-624-5p overexpression inhibited CAF proliferation and collagen contraction (p < 0.01) and reduced the proliferation, migration, and invasion capabilities of A549 and PC9 cells (p < 0.001). Mechanistically, miR-624-5p bound to FAP mRNA and negatively regulated FAP expression (p < 0.001), thus suppressing CAF activation and tumor metastasis. Conclusions: Our findings establish miR-624-5p as a novel upstream regulator that suppresses FAP expression, consequently inhibiting CAF activation and its pro-metastatic function. Targeting the miR-624-5p/FAP axis represents a promising therapeutic strategy for NSCLC metastasis.
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(This article belongs to the Special Issue Lung Cancer: Updates on Therapy and Prognostic Prediction)
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Clinical Impact of EGFR Mutation Subtypes on Treatment Outcomes in Advanced Non-Small Cell Lung Cancer: An Austrian Real-World Study
by
Caroline Braschel, Hannah Fabikan, Vania Mikaela Rodriguez, Maximilian J. Hochmair, Oliver Illini, Leyla Ay, Christoph Weinlinger, Julie Krainer-Jacobs, Nino Müser, Arschang Valipour and Dagmar Krenbek
Cancers 2026, 18(2), 278; https://doi.org/10.3390/cancers18020278 - 16 Jan 2026
Abstract
Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR
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Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence of EGFR mutations was 11% (145 out of 1267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4–24.9) and 14.2 months (95% CI: 7.4–20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, the EGFR common mutation subtype (HR = 3.71 95%CI: 1.23–11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18–21. Conclusions: The results underscore the prognostic role of distinct EGFR genotypes and the urgency of determining the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mutations and the resulting need for further research to investigate alternative treatment options.
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(This article belongs to the Special Issue EGFR-Tyrosine Kinase Inhibitor (EGFR-TKI) for Non-Small Cell Lung Cancer)
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