Cancers

25 pages, 2813 KB

Open AccessReview

PSMA-Based Radiopharmaceuticals in Prostate Cancer Theranostics: Imaging, Clinical Advances, and Future Directions

by Ali Cahid Civelek

Cancers 2026, 18(2), 234; https://doi.org/10.3390/cancers18020234 - 12 Jan 2026

Prostate cancer remains one of the most common malignancies in men worldwide, with incidence and mortality steadily increasing across diverse populations. While early detection and radical prostatectomy can achieve durable control in a subset of patients, approximately 40% of men will ultimately experience [...] Read more.

Prostate cancer remains one of the most common malignancies in men worldwide, with incidence and mortality steadily increasing across diverse populations. While early detection and radical prostatectomy can achieve durable control in a subset of patients, approximately 40% of men will ultimately experience biochemical recurrence often in the absence of clinically detectable disease. Conventional imaging approaches—CT, MRI, and bone scintigraphy—have limited sensitivity for early relapses, frequently leading to delayed diagnosis and suboptimal treatment planning. The discovery of prostate-specific membrane antigen (PSMA) in 1987 and its subsequent clinical translation into positron emission tomography (PET) imaging with [⁶⁸Ga]Ga-PSMA-11 in 2012, followed by U.S. FDA approval in 2020, has transformed the landscape of prostate cancer imaging. PSMA PET has demonstrated superior accuracy over conventional imaging, as highlighted in the landmark proPSMA trial and now serves as the foundation for theranostic approaches that integrate diagnostic imaging with targeted radioligand therapy. The clinical approval of [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto^®: (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) has established targeted radioligand therapy as a viable option for men with metastatic castration-resistant prostate cancer, extending survival in patients with limited alternatives. Emerging strategies, including next-generation ligands with improved tumor uptake and altered clearance pathways, as well as the integration of artificial intelligence for imaging quantification, are poised to further refine patient selection, dosimetry, and treatment outcomes. This review highlights the evolution of PSMA-based imaging and therapy, discusses current clinical applications and limitations, and outlines future directions for optimizing theranostic strategies in prostate cancer care. Full article

(This article belongs to the Section Cancer Therapy)

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21 pages, 13737 KB

Open AccessArticle

Adipose Stromal Cell-Derived Cancer-Associated Fibroblasts Promote Pancreatic Adenocarcinoma Progression Through SFRP4 Signaling

by Joseph Rupert, Lingyi Cai, Alexes C. Daquinag, Dimitris Anastassiou and Mikhail G. Kolonin

Cancers 2026, 18(2), 233; https://doi.org/10.3390/cancers18020233 - 12 Jan 2026

Abstract

Background/objectives: Progression of pancreatic ductal adenocarcinoma (PDAC) and other carcinomas relies on cancer-associated fibroblasts (CAFs). A subset of CAFs is derived from adipose stromal cells (ASCs) recruited by tumors and the ASC-CAF conversion has been associated with invasiveness and poor prognosis. Methods: To [...] Read more.

Background/objectives: Progression of pancreatic ductal adenocarcinoma (PDAC) and other carcinomas relies on cancer-associated fibroblasts (CAFs). A subset of CAFs is derived from adipose stromal cells (ASCs) recruited by tumors and the ASC-CAF conversion has been associated with invasiveness and poor prognosis. Methods: To explore the underlying molecular mechanisms, we used a model based on primary ASCs derived from human visceral adipose tissue co-cultured with human PDAC cell line Capan-1. To investigate cancer progression in vivo, we also used mice orthotopically grafted with mouse KPC cells. Results: Genomic analysis revealed that Capan-1 co-culture induces Wnt and TGFβ signaling and extracellular matrix (ECM) gene expression in ASC. We investigated the function of two markers of the fibroblastic transition highly induced by cancer cells: a long non-coding RNA LINC01614 and a Wnt signaling modulator SFRP4. By using ASCs with either SFRP4 or LINC01614 knocked out (ko), we showed that both genes are required for Wnt/TGFβ signaling and ECM induction in ASCs by Capan-1. Analysis of changes in Capan-1 genes that rely on LINC01614 and SFRP4 expression in ASCs also identified the Wnt and TGF pathways. SFRP4 ko in ASCs suppressed both migration and invasion of Capan-1 cells. We show that tumors in SFRP4 ko mice have less desmoplasia, less epithelial dedifferentiation, reduced growth rate, and reduced progression to metastasis. Conclusions: We conclude that SFRP4 promotes cancer progression in pancreatic cancer and is a promising therapeutic target. Full article

(This article belongs to the Special Issue Targeting Tumor Microenvironment in Cancer: An Impact on Therapeutic Efficacy)

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3 pages, 165 KB

Open AccessCorrection

Correction: Morishita et al. MicroRNAs in the Pathogenesis of Hepatocellular Carcinoma: A Review. Cancers 2021, 13, 514

by Asahiro Morishita, Kyoko Oura, Tomoko Tadokoro, Koji Fujita, Joji Tani and Tsutomu Masaki

Cancers 2026, 18(2), 232; https://doi.org/10.3390/cancers18020232 - 12 Jan 2026

Abstract

Following publication [...] Full article

(This article belongs to the Collection Regulatory and Non-Coding RNAs in Cancer Epigenetic Mechanisms)

4 pages, 155 KB

Open AccessEditorial

Challenges in the Care of Cancer Patients in Emergency Departments

by Thomas Licht

Cancers 2026, 18(2), 231; https://doi.org/10.3390/cancers18020231 - 12 Jan 2026

Abstract

Cancer patients often suffer complications from their underlying disease or from adverse effects of their oncologic therapies [...] Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

12 pages, 266 KB

Open AccessReview

Treatment of Periprosthetic Joint Infection After Tumor Megaprosthetic Reconstruction: A Narrative Review

by Wei Wang, Haoran Qiao, Zhiqing Zhao and Taiqiang Yan

Cancers 2026, 18(2), 230; https://doi.org/10.3390/cancers18020230 - 12 Jan 2026

Abstract

Purpose: Periprosthetic joint infection (PJI) is a devastating complication following limb salvage surgery with tumor megaprosthetic reconstruction, leading to high morbidity and complex management. Despite advancements in prosthesis design and materials, infection rates are notably higher than in conventional arthroplasty. This narrative review [...] Read more.

Purpose: Periprosthetic joint infection (PJI) is a devastating complication following limb salvage surgery with tumor megaprosthetic reconstruction, leading to high morbidity and complex management. Despite advancements in prosthesis design and materials, infection rates are notably higher than in conventional arthroplasty. This narrative review synthesizes current evidence on the etiology, diagnosis, and management of PJIs in this unique setting. Methods: We conducted narrative review of literature from PubMed and Embase using keywords related to PJIs and tumor megaprostheses, aiming to summarize risk factors, diagnostic criteria, pathogen profiles, and treatment outcomes. Results: Key findings indicate that the risk of PJI is multifactorial, involving patient-related, disease-related, and treatment-related factors. Diagnosis relies on a combination of clinical presentation, serological markers, imaging, and microbiological studies, though established criteria for conventional PJI may require adaptation for tumor cases. Treatment strategies include irrigation and debridement (I&D), debridement, antibiotics, implant retention with modular component exchange (DAIR), one-stage or two-stage revision, and amputation. Success rates vary, and optimal management requires a multidisciplinary, individualized approach. However, two-stage revision is considered the gold standard for chronic PJIs. Conclusions: PJIs after tumor megaprosthetic reconstruction presents distinct challenges. Management requires a multidisciplinary, individualized approach. Future research should focus on validated diagnostic criteria for this population, novel anti-biofilm strategies, and standardized treatment protocols. Full article

(This article belongs to the Special Issue Clinical and Surgical Outcomes in the Management of Extremity Soft Tissue Sarcomas (2nd Edition))

23 pages, 4491 KB

Open AccessArticle

Steroid Phenotype Stratification Reveals Distinct HLA Expression Signatures in Adrenocortical Carcinoma

by Igor S. Giner, Jean S. S. Resende, João C. D. Muzzi, José A. M. Barbuto, Enzo Lalli, Mauro A. A. Castro and Bonald C. Figueiredo

Cancers 2026, 18(2), 229; https://doi.org/10.3390/cancers18020229 - 12 Jan 2026

Abstract

Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy where endogenous steroid excess may foster immune evasion. However, whether this hormonal axis directly modulates the antigen presentation machinery remains unclear. Methods: We applied an immunoinformatics approach to the TCGA-ACC cohort ( [...] Read more.

Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy where endogenous steroid excess may foster immune evasion. However, whether this hormonal axis directly modulates the antigen presentation machinery remains unclear. Methods: We applied an immunoinformatics approach to the TCGA-ACC cohort (n = 79) to investigate relationships among steroid phenotype, HLA expression, tumor microenvironment (TME), and patient outcome. Key findings were assessed in an independent validation cohort (ENSAT-ACC, n = 44) using C1A/C1B molecular subtypes corresponding to the steroid phenotypes. Results: Stratification by steroid phenotype revealed two distinct immunological profiles. The high steroid production (HSP) phenotype was associated with suppressed HLA expression and a lymphocyte-depleted “cold” TME. In contrast, the low steroid production (LSP) phenotype displayed elevated HLA expression, enriched T-cell infiltration, and upregulation of immune checkpoints (e.g., PDCD1, CTLA4), consistent with an inflamed but exhausted TME. The core signature of HLA downregulation in the HSP-like phenotype (C1A) and the significant survival advantage of the LSP-like phenotype (C1B) were confirmed in the validation cohort, demonstrating biological robustness despite platform and sample size differences. Conclusions: These findings identify the steroid phenotype as a critical regulator of immune escape in ACC. Our results support incorporating this stratification as a biomarker for patient selection, identifying LSP tumors as the subgroup most likely to benefit from immune checkpoint blockade due to their “hot” yet exhausted microenvironment. Full article

(This article belongs to the Special Issue Advances in the Immunotherapy of Metastatic Cancer)

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11 pages, 1113 KB

Open AccessArticle

Rapid Assessment of Tumor Thickness in Cutaneous Squamous Cell Carcinoma Using Ex Vivo Confocal Microscopy

by Daniela Hartmann, Katharina Wex, Aimée Braun, Paulina Pabst, Alisa Swarlik, Lisa Buttgereit, Lara Stärr, Andreas Ohlmann, Elke C. Sattler and Maximilian Deußing

Cancers 2026, 18(2), 228; https://doi.org/10.3390/cancers18020228 - 12 Jan 2026

Abstract

Objectives: Ex vivo confocal laser scanning microscopy (EVCM) is a pioneering diagnostic method that enables fresh tissue samples to be analyzed directly during surgery. For the assessment of non-melanocytic skin cancer (NMSC), including cutaneous squamous cell carcinoma (cSCC), it provides a rapid [...] Read more.

Objectives: Ex vivo confocal laser scanning microscopy (EVCM) is a pioneering diagnostic method that enables fresh tissue samples to be analyzed directly during surgery. For the assessment of non-melanocytic skin cancer (NMSC), including cutaneous squamous cell carcinoma (cSCC), it provides a rapid addition to conventional histology. While previous studies have shown that EVCM reliably identifies the morphological features of cSCCs, quantitative criteria such as tumor thickness have not yet been systematically evaluated. This study investigated whether EVCM can be used to accurately and reproducibly measure the thickness of cSCCs, an important parameter for predicting metastatic risk. Methods: Eighty-two histologically verified cSCCs from different anatomical sites were assessed by the current gold standard of histopathology and EVCM. A statistical comparison of the confocal tumor thickness (CTT) and the histopathological tumor thickness (HTT) was then performed. In addition, it was analyzed how reliable EVCM was in the assignment of cSCCs to the correct tumor thickness category. Results: There was a very high agreement between both methods, evidenced by a Spearman correlation coefficient of 0.94 and a coefficient of determination of 0.859. Overall, 95.1% of the samples were correctly classified into the appropriate tumor thickness category using EVCM. Cohen’s Kappa of 0.90 indicated almost perfect agreement between EVCM and histology. Conclusions: These findings demonstrate that EVCM is a precise and reliable method for determining tumor thickness and the corresponding category in cSCCs. It enables immediate intraoperative assessment of the metastatic risk and preliminary classification of low-risk tumors. Additional studies with larger patient cohorts are required to further validate these results and support clinical implementation. Full article

(This article belongs to the Special Issue Digital Pathology in Precision Oncology: Emerging Tools for Diagnosis and Treatment Guidance)

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16 pages, 1282 KB

Open AccessArticle

Refining Outcomes in Technically Resectable Colorectal Liver Metastases: A Simplified Risk Model and the Role of Preoperative Chemotherapy

by Kou Kanesada, Masao Nakajima, Tatsuya Ioka, Shinobu Tomochika, Yoshitaro Shindo, Yukio Tokumitsu, Hiroto Matsui, Hironori Tanaka, Yuki Nakagami, Ryouichi Tsunedomi, Michihisa Iida, Hidenori Takahashi and Hiroaki Nagano

Cancers 2026, 18(2), 227; https://doi.org/10.3390/cancers18020227 - 12 Jan 2026

Abstract

Background: Preoperative chemotherapy is increasingly used for colorectal liver metastases (CRLM), but simple risk stratification tools for routine practice remain limited. We developed a simple risk model to predict outcomes after curative-intent CRLM resection, including in patients receiving preoperative chemotherapy. Methods: [...] Read more.

Background: Preoperative chemotherapy is increasingly used for colorectal liver metastases (CRLM), but simple risk stratification tools for routine practice remain limited. We developed a simple risk model to predict outcomes after curative-intent CRLM resection, including in patients receiving preoperative chemotherapy. Methods: We retrospectively analyzed 115 patients who underwent initial curative-intent liver resection for CRLM at two centers. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were evaluated using Cox proportional hazards models and log-rank tests. Model performance was benchmarked against the Beppu nomogram and Fong’s clinical risk score using the area under the curve (AUC). Outcomes were also assessed based on response to preoperative chemotherapy. Results: Having ≥3 CRLMs was the only independent predictor common to both OS and RFS. Among patients with 1–2 CRLMs, the largest tumor diameter being ≥5 cm independently predicted RFS. A composite high-risk definition (≥3 CRLMs, or 1–2 CRLMs with a diameter ≥ 5 cm) independently predicted recurrence (HR 2.05, p = 0.007) and overall mortality (HR 2.24, p = 0.017). The AUCs were similar to the Beppu nomogram for recurrence (0.68 vs. 0.70 (p = 0.683) at 36 months, 0.66 vs. 0.68 (p = 0.766) at 60 months) and to Fong’s score for survival (0.59 vs. 0.64 (p = 0.430) at 36 months, 0.65 vs. 0.74 (p = 0.074) at 60 months). Among patients receiving preoperative chemotherapy (n = 72), high-risk status was associated with poorer RFS (HR 3.11, p < 0.001) and OS (HR 2.80, p = 0.010). Within this subgroup, progressive disease (PD) was associated with worse outcomes than disease control (CR/PR/SD). Conclusions: This two-variable, rule-based model provides an easy-to-use tool for postoperative risk stratification after CRLM resection, and incorporating chemotherapy response may further refine prognostication. Full article

(This article belongs to the Special Issue Chemo-Radio-Immunotherapy for Colorectal Cancer)

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18 pages, 1418 KB

Open AccessArticle

Breathprints for Breast Cancer: Evaluating a Non-Invasive Approach to BI-RADS 4 Risk Stratification in a Preliminary Study

by Ashok Prabhu Masilamani, Jayden K Hooper, Md Hafizur Rahman, Romy Philip, Palash Kaushik, Geoffrey Graham, Helene Yockell-Lelievre, Mojtaba Khomami Abadi and Sarkis H. Meterissian

Cancers 2026, 18(2), 226; https://doi.org/10.3390/cancers18020226 - 11 Jan 2026

Abstract

Background/Objectives: Breast cancer is the most common malignancy among women, and early detection is critical for improving outcomes. The Breast Imaging Reporting and Data System (BI-RADS) standardizes reporting, but the BI-RADS 4 category presents a major challenge, with malignancy risk ranging from [...] Read more.

Background/Objectives: Breast cancer is the most common malignancy among women, and early detection is critical for improving outcomes. The Breast Imaging Reporting and Data System (BI-RADS) standardizes reporting, but the BI-RADS 4 category presents a major challenge, with malignancy risk ranging from 2% to 95%. Consequently, most women in this category undergo biopsies that ultimately prove unnecessary. This study evaluated whether exhaled breath analysis could distinguish malignant from benign findings in BI-RADS 4 patients. Methods: Participants referred to the McGill University Health Centre Breast Center with BI-RADS 3–5 findings provided multiple breath specimens. Breathprints were captured using an electronic nose (eNose) powered breathalyzer, and diagnoses were confirmed by imaging and pathology. An autoencoder-based model fused the breath data with BI-RADS scores to predict malignancy. Model performance was assessed using repeated cross-validation with ensemble voting, prioritizing sensitivity to minimize false negatives. Results: The breath specimens of eighty-five participants, including sixty-eight patients with biopsy-confirmed benign lesions and seventeen patients with biopsy-confirmed breast cancer within the BI-RADS 4 cohort were analyzed. The model achieved a mean sensitivity of 88%, specificity of 75%, and a negative predictive value (NPV) of 97%. Results were consistent across BI-RADS 4 subcategories, with particularly strong sensitivity in higher-risk groups. Conclusions: This proof-of-concept study shows that exhaled breath analysis can reliably differentiate malignant from benign findings in BI-RADS 4 patients. With its high negative predictive value, this approach may serve as a non-invasive rule-out tool to reduce unnecessary biopsies, lessen patient burden, and improve diagnostic decision-making. Larger, multi-center studies are warranted. Full article

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

14 pages, 353 KB

Open AccessArticle

The Role of TARE for Bridging and Downstaging of HCC Before Resection or Liver Transplant

by Abdullah Alshamrani, Sung Ki Cho, Namkee Oh, Jinsoo Rhu, Gyu-Seong Choi, Dong-Ho Hyun and Jongman Kim

Cancers 2026, 18(2), 225; https://doi.org/10.3390/cancers18020225 - 11 Jan 2026

Abstract

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Transarterial radioembolization (TARE) has emerged as a locoregional therapy to downstage tumors and expand surgical eligibility. Methods: This retrospective study included patients with HCC who underwent TARE as a bridging [...] Read more.

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Transarterial radioembolization (TARE) has emerged as a locoregional therapy to downstage tumors and expand surgical eligibility. Methods: This retrospective study included patients with HCC who underwent TARE as a bridging treatment. The primary outcomes assessed were the efficacy of TARE in facilitating curative surgery and long-term oncological outcomes, specifically overall survival (OS) and disease-free survival (DFS). Results: This study included 25 patients. 17 patients subsequently underwent surgical resection and eight underwent living-donor liver transplantation (LDLT). At a median follow-up of 33.4 months, the median disease-free survival (DFS) was 11.2 months. Patients with recurrence had a median DFS of 3.65 months, and those without recurrence had a median DFS of 27.1 months. The median overall survival (OS) for the cohort was 33.4 months. At the last follow-up, 76% of patients were alive and disease-free. Kaplan–Meier analysis demonstrated sustained OS in the LDLT group, while resection patients gradually declined within the first two years. Conclusions: TARE is an effective bridging strategy that enables curative-intent surgery in selected patients with HCC and supports favorable long-term oncological outcomes. Careful patient selection and multidisciplinary management remain essential to optimize survival benefits. Full article

(This article belongs to the Special Issue Surgical Treatment of Hepatocellular Carcinoma)

16 pages, 2728 KB

Open AccessReview

Advancements in Preclinical Models for NF2-Related Schwannomatosis Research

by Bo-Shi Zhang, Simeng Lu, Scott R. Plotkin and Lei Xu

Cancers 2026, 18(2), 224; https://doi.org/10.3390/cancers18020224 - 11 Jan 2026

Abstract

NF2-related Schwannomatosis (NF2-SWN) remains a disorder with few effective treatment options. Patients develop vestibular schwannomas (VSs) on both auditory nerves, which gradually impair hearing and often result in significant communication difficulties, social withdrawal, and higher rates of depression. Progress in [...] Read more.

NF2-related Schwannomatosis (NF2-SWN) remains a disorder with few effective treatment options. Patients develop vestibular schwannomas (VSs) on both auditory nerves, which gradually impair hearing and often result in significant communication difficulties, social withdrawal, and higher rates of depression. Progress in understanding NF2-SWN biology and translating discoveries into therapies has been slowed by the absence of robust animal models that faithfully reproduce both tumor behavior and the associated neurological deficits. In this review, we summarized the development of animal models that not only reproduce tumor growth in the peripheral nerve microenvironment but also reproduce tumor-induced neurological symptoms, such as hearing loss and ataxia. We further highlight the currently available organotypic models for NF2-SWN. Together, these systems provide an essential foundation for advancing mechanistic studies and accelerating the development of effective therapies for this devastating disorder. Full article

(This article belongs to the Special Issue Advancements in Preclinical Models for Solid Cancers)

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13 pages, 1007 KB

Open AccessArticle

Pathological Complete Response in Rectal Cancer Patients: A Correlation Between Pathological and Clinical Stage and Oncological Outcome

by Ana Grigoraș, Dragoș-Viorel Scripcariu, Ionuț Huțanu, Bogdan Filip, Mihaela-Mădălina Gavrilescu, Maria-Gabriela Aniței, Gheorghe Bălan and Viorel Scripcariu

Cancers 2026, 18(2), 223; https://doi.org/10.3390/cancers18020223 - 11 Jan 2026

Abstract

Introduction: In rectal cancer, the choice of treatment strategy depends on the tumor stage and the response to neoadjuvant therapy. Accurate assessment of tumor regression through magnetic resonance imaging (MRI) may help to guide personalized approaches, including delayed or nonoperative management. This study [...] Read more.

Introduction: In rectal cancer, the choice of treatment strategy depends on the tumor stage and the response to neoadjuvant therapy. Accurate assessment of tumor regression through magnetic resonance imaging (MRI) may help to guide personalized approaches, including delayed or nonoperative management. This study aimed to assess the correlations between pathological complete response (pCR) and clinical staging before and after neoadjuvant treatment in rectal cancer patients. Methods: We conducted a retrospective analysis of rectal cancer patients treated with neoadjuvant therapy followed by radical resection in our oncological surgery department between July 2012 and December 2024. Clinical staging and tumor response were assessed using MRI, focusing on T- and N-stage evaluation. Pathological complete response (pCR) was defined as the absence of tumor cells on histopathological examination. Associations between pCR and clinical variables were explored. Results: Out of a total of 1693 rectal cancer patients, 783 (46.25%) received neoadjuvant therapy, with 62 patients (7.92%) presenting pCR. The majority had tumor stage cT3 (n = 45, 72.6%) and lymph node stage cN2b (n = 25, 40.3%) before treatment. Post-treatment MRI showed complete tumor response (T0) in 20 patients (32.3%) and nodal downstaging to N0 in 34 patients (54.8%). MRI provided imaging findings that indicate a limited correlation between clinical assessment of tumor response and pathological outcome. Six patients (9.6%) developed distant metastases, and there were no local recurrences. Conclusions: While MRI provides valuable preoperative information, its accuracy in predicting pCR remains limited. Achieving pCR is a favorable prognostic indicator, but it does not eliminate the risk of distant metastasis; therefore, continued surveillance and individualized management strategies remain essential to optimize outcomes in rectal cancer patients. Full article

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

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13 pages, 1491 KB

Open AccessArticle

Sarcopenia Predicts Mortality in Bladder Cancer with Neoadjuvant Chemotherapy: A Multicenter Study

by Alice Pitout, Charles Mazeaud, Alicia Blondeau, Julia Salleron, Vincent Massard and Aurélien Lambert

Cancers 2026, 18(2), 222; https://doi.org/10.3390/cancers18020222 - 11 Jan 2026

Abstract

Background: Sarcopenia is a recognized adverse prognostic factor in many cancers and can be reliably assessed using computed tomography (CT) scans. Its prognostic value in bladder cancer patients undergoing neoadjuvant chemotherapy remains underexplored. This study aimed to assess sarcopenia’s impact on survival and [...] Read more.

Background: Sarcopenia is a recognized adverse prognostic factor in many cancers and can be reliably assessed using computed tomography (CT) scans. Its prognostic value in bladder cancer patients undergoing neoadjuvant chemotherapy remains underexplored. This study aimed to assess sarcopenia’s impact on survival and compare different measurement thresholds. Methods: We conducted a retrospective multicenter study including patients with invasive urothelial carcinoma treated with neoadjuvant chemotherapy followed by cystectomy between 2015 and 2021. Sarcopenia was assessed by measuring the Skeletal Muscle Index on CT scans before chemotherapy (BC) and prior to surgery (BS). The primary endpoint was overall survival. Secondary endpoints included progression-free survival (PFS), pathological complete response (pCR), and treatment-related complications. Results: Seventy-four patients were included, the majority receiving the MVAC regimen (71.7%). Forty percent of patients achieved a pCR, 35% experienced disease recurrence, and the median PFS was 25 months. Sarcopenia was observed in 27% of patients BC and in 39% BS. Sarcopenia was associated with an increased risk of all-cause mortality: BC according to the definition by Martin et al. (HR 3.38; 95% CI [1.25–9.12]; p = 0.016) and Fearon et al. (HR 4.03; 95% CI [1.13–14.3]; p = 0.031); and BS according to Martin et al. (HR 3.7; 95% CI [1.12–12.2]; p = 0.032) and Fearon et al. (HR 6.08; 95% CI [1.48–24.9]; p = 0.012). Sarcopenia was an independent risk factor of shorter PFS. Conclusions: Sarcopenia represent an independent and reproducible prognostic factor for mortality in patients with bladder cancer. The study is the first study to compare threshold values at different time points. Full article

(This article belongs to the Section Cancer Therapy)

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22 pages, 2306 KB

Open AccessArticle

The Diagnostic Trap in Radiation-Induced Mesothelioma: Kinetic-Morphological Decoupling Masks Molecular Aggression

by Norikatsu Fujita, Katsumi Fujita, Hironobu Osumi and Yoshiyasu Takefuji

Cancers 2026, 18(2), 221; https://doi.org/10.3390/cancers18020221 - 9 Jan 2026

Abstract

Background: In malignant pleural mesothelioma, epithelioid histology is traditionally considered a favorable prognostic marker. However, it remains clinically undetermined whether the intensity of an oncogenic insult can disrupt this link. Radiation-induced cases serve as an unconfounded biological model to dissect such trajectories masked [...] Read more.

Background: In malignant pleural mesothelioma, epithelioid histology is traditionally considered a favorable prognostic marker. However, it remains clinically undetermined whether the intensity of an oncogenic insult can disrupt this link. Radiation-induced cases serve as an unconfounded biological model to dissect such trajectories masked by asbestos confounding. Methods: We performed an Individual Patient Data (IPD) synthesis of 20 strictly asbestos-unexposed human cases, applying clinically established dose stratification (intermediate: 20–45 Gy vs. high: >45 Gy). To confirm the observed pattern, we examined data from 829 dogs in the Colorado State University (CSU) Beagle Study. Results: In the intermediate-dose group (n = 13), a significant positive correlation persisted between age at radiotherapy and the latent period (ρ = 0.567, p = 0.043). Conversely, high-dose exposure (>45 Gy) showed a disruption of this age-dependent pattern, with a trend toward inverse correlation (ρ = −0.754, p = 0.084). Interaction analysis confirmed a statistically significant divergence between these dose-dependent trends (p = 0.005). The CSU Beagle Study (n = 829) demonstrated the physical basis of this phenomenon: in the canine model, high-dose exposure (≥0.74 Gy) triggered a “Step-Jump” in cumulative incidence (30.4% at 0.5 years), indicating instantaneous carcinogenic onset distinct from cumulative biological aging. Conclusions: This kinetic divergence points to a “Diagnostic Trap.” We propose a ‘Single- to Double-Brake’ framework where intermediate doses preserve age-dependent progression, whereas high doses likely trigger catastrophic genomic failure (chromothripsis) that bypasses the time required for morphological dedifferentiation. Consequently, morphologically indolent epithelioid tumors in high-dose survivors may harbor aggressive molecular profiles not predicted by histology alone, necessitating risk-stratified precision surveillance. Full article

(This article belongs to the Special Issue Emerging Concepts in Mesothelioma)

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15 pages, 2473 KB

Open AccessArticle

CV1 Chimpanzee Adenovirus Efficiently Transduces Mesenchymal Stem and Leukemia Cells: Implications for Cellular Targeting and Vector Tropism

by Lorella Tripodi, Maria Vitale, Barbara Izzo, Filippo Scialò, Barbara Lombardo and Lucio Pastore

Cancers 2026, 18(2), 220; https://doi.org/10.3390/cancers18020220 - 9 Jan 2026

Abstract

Objectives: Adenoviruses (Ads) are among the most used vectors for gene therapy; human Ad serotype 5-derived (HuAd5) vectors are the most frequently used for gene transfer applications. However, Ad5 infection is endemic in humans, and 20% of the Western population has neutralizing antibodies [...] Read more.

Objectives: Adenoviruses (Ads) are among the most used vectors for gene therapy; human Ad serotype 5-derived (HuAd5) vectors are the most frequently used for gene transfer applications. However, Ad5 infection is endemic in humans, and 20% of the Western population has neutralizing antibodies (nAbs). Pre-existing immunity against HuAd5 represents a major issue for many gene therapy applications. In our study, we evaluated several Ad serotypes derived from chimpanzees (ChAds) in vitro and in vivo to assess their transduction efficiency in various cell types and tissues. We aimed at identifying Ad serotypes able either to transduce “challenging” cell types or to represent a possible alternative to Ad5-derived vectors with comparable infectivity and tropism. Methods: We evaluated the efficacy of transduction of twelve ChAds vectors expressing enhanced green fluorescent protein (EGFP) in human embryonic kidney cells, as well as human leukemic and human mesenchymal stem cells, using flow cytometry to determine the percentage of EGFP-expressing cells and their mean fluorescent intensity (MFI). We observed the highest transduction efficiency in the serotype CV1 ChAd; therefore, we proceeded to evaluate toxicity and biodistribution in vivo. Results: After in vitro evaluation of twelve ChAds serotypes, we observed that the CV1 serotype was the most efficient in transducing both leukemia cell lines (HL-60 and NB-4) and human mesenchymal stem cells. Furthermore, in vivo analysis of the CV1 serotype induced an inflammatory reaction similar to what was observed after HuAd5 administration. Conclusions: ChAds vectors represent an effective alternative for the transduction of cells resistant to HuAd5 infection, such as mesenchymal stem cells and leukemic cells. In addition, we observed that the CV1 ChAd serotype presented a transduction profile similar to HuAd5 in vitro and induced a similar inflammatory response in vivo; therefore, CV1 ChAd-derived vectors represent an interesting alternative for gene therapy applications. Full article

(This article belongs to the Special Issue New Insights into Cancer Immunotherapy: From Immune Cell to Clinical Practice)

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18 pages, 1407 KB

Open AccessArticle

Protocol Development for the Korean Survey for Cancer Survivorship and Preliminary Analysis of Employment Change’s Impact on Quality of Life and Psychological Health

by Janine Marie Balbedina, Yeol Kim, Hye Joo Jang, Ha Yeong You, Jae Hyun Park, Hyun Woo Lee, Ji Soo Park, Yu Ri Choe and Kyu Won Jung

Cancers 2026, 18(2), 219; https://doi.org/10.3390/cancers18020219 - 9 Jan 2026

Abstract

Background/Objectives: The Korean Survey for Cancer Survivorship (KSCS) aims to comprehensively assess cancer survivors’ health behaviors, quality of life (QoL), and socioeconomic challenges. This study evaluated the feasibility of the KSCS protocol and identified key factors influencing psychological health and QoL among [...] Read more.

Background/Objectives: The Korean Survey for Cancer Survivorship (KSCS) aims to comprehensively assess cancer survivors’ health behaviors, quality of life (QoL), and socioeconomic challenges. This study evaluated the feasibility of the KSCS protocol and identified key factors influencing psychological health and QoL among cancer survivors. Methods: The nationwide survey targeted survivors diagnosed with breast, colorectal, liver, lung, stomach, prostate, and gynecological cancers who had completed active treatment within 1 to 10 years. The respondents were given the option to participate in the survey either online or in-person. The questionnaire has 229 questions, including internationally validated tools such as the EQ-5D-3L, PHQ-9, and GAD-7. Results: A total of 983 cancer survivors completed the survey (92.7% online, 8.3% in-person) and were categorized by post-diagnosis duration. Survivors diagnosed within 1–3 years reported higher rates of moderate-severe depression (11.4% vs. 8.3%), moderate-severe anxiety (5.9% vs. 5.1%), and poorest QoL (63.0% vs. 50.9%) compared to those diagnosed more than 5 years ago. Employment changes, such as loss of job, change of workplace, or work leave, were significantly associated with worse health outcomes, including higher rates of moderate-severe depression (OR = 4.39; 95% CI 2.43–7.96), moderate-severe anxiety (OR = 3.63; 95% CI 1.68–0.88), and having extreme QoL problems (OR = 6.37; 95% CI 2.03–20.00). Conclusions: The KSCS protocol is feasible for nationwide implementation and provides comprehensive data on health, psychological, and socioeconomic challenges among cancer survivors. Preliminary findings highlight employment’s critical role in cancer survivors’ well-being and the need for survivorship care that integrates socioeconomic and clinical factors. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

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15 pages, 979 KB

Open AccessArticle

Small Bowel Gastrointestinal Stromal Tumors: A 15-Year Cohort Study Focusing on Jejuno-Ileal Site-Specific Outcomes and Prognostic Factors

by Yuichi Kojima, Kentaro Tominaga, Yuzo Kawata, Chizuru Kaneko, Shuhei Kondo, Yoshifumi Shimada, Junji Yokoyama, Toshifumi Wakai and Shuji Terai

Cancers 2026, 18(2), 218; https://doi.org/10.3390/cancers18020218 - 9 Jan 2026

Abstract

Background: Site-specific long-term outcomes, including neurofibromatosis type 1 (NF1), Ki-67 prognostic value, and very late recurrences of small bowel gastrointestinal stromal tumors (GISTs), remain inadequately defined. Methods: This retrospective cohort study investigated the clinical characteristics, diagnostic challenges, and long-term outcomes of patients with [...] Read more.

Background: Site-specific long-term outcomes, including neurofibromatosis type 1 (NF1), Ki-67 prognostic value, and very late recurrences of small bowel gastrointestinal stromal tumors (GISTs), remain inadequately defined. Methods: This retrospective cohort study investigated the clinical characteristics, diagnostic challenges, and long-term outcomes of patients with small bowel GISTs. This retrospective, single-center study (2008–2024) analyzed 27 consecutive patients (average age: 62.2 years) with jejunal/ileal GISTs. Clinicopathologic features, diagnostic yield of balloon-assisted enteroscopy (BAE), treatments, and outcomes were evaluated during a 10.2-year median follow-up period. Recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan–Meier with log-rank testing. Ki-67 was assessed using MIB-1; a prespecified 5% cut-off was chosen based on prior evidence. Results: Tumor (mean size, 62.4 mm) sites included the jejunum (74.1%) and ileum (25.9%). NF1 was present in 3/27 (11.1%) patients, all with multiple jejunal tumors. Among the 14 patients who underwent BAE, biopsy was attempted in six and yielded a histological diagnosis in one (16.7%). Six patients had recurrence; two died from disease >10 years postoperatively. Five-year OS and RFS were 91.3% and 68.7%, respectively. Adverse RFS was associated with ileal location (p = 0.03), size ≥ 10 cm (p < 0.001), mitoses > 5/50 high-power fields (p = 0.002), and Ki-67 ≥ 5% (p < 0.001). One patient labeled low risk by conventional models had recurrence with Ki-67 = 10%. Another classified as low risk by conventional models experienced recurrence >10 years after surgery, with a Ki-67 index of 10%. Conclusions: Extended, risk-adapted surveillance may be reasonable for small-bowel GISTs, and it may be beneficial to incorporate Ki-67 (≥5%) into site-based risk stratification. These observations remain hypothesis-generating and require validation in larger, multicenter cohorts and prospective studies. Full article

(This article belongs to the Section Cancer Therapy)

18 pages, 953 KB

Open AccessReview

The Role of Low CD36 Expression in the Development of Non-Small Cell Lung Cancer and Its Potential for Therapy

by Ran Wu, Xiaohong Xu, Danju Luo, Junhua Wu, Xiaona Chang, Chenggong Ma, Bo Huang, Jun Fan and Xiu Nie

Cancers 2026, 18(2), 217; https://doi.org/10.3390/cancers18020217 - 9 Jan 2026

Abstract

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. NSCLC, which constitutes approximately 85% of cases, continues to exhibit a poor prognosis despite advancements in therapeutic interventions, underscoring the urgent necessity to elucidate its molecular mechanisms and identify novel therapeutic [...] Read more.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. NSCLC, which constitutes approximately 85% of cases, continues to exhibit a poor prognosis despite advancements in therapeutic interventions, underscoring the urgent necessity to elucidate its molecular mechanisms and identify novel therapeutic targets. CD36, a multifunctional transmembrane glycoprotein, is integral to lipid uptake, immune recognition, inflammatory regulation, molecular adhesion, and apoptosis. Increasing evidence implicates CD36 in the progression of various cancers. In the context of lung cancer, CD36 facilitates tumorigenesis through multiple pathways, including the remodeling of tumor cell lipid metabolism, reprogramming of tumor-associated macrophages, and modulation of immune cell functions such as those of Tregs and CD8⁺ T cells. Additionally, CD36 is intricately linked with the function of cancer-associated fibroblasts and the remodeling of the tumor stromal microvasculature. This systematic review synthesizes the mechanisms by which CD36 contributes to NSCLC proliferation, migration, epithelial–mesenchymal transition, and modulation of the tumor microenvironment. Furthermore, we explore emerging therapeutic strategies that target CD36. Regulating CD36 expression effectively intervenes in the malignant behavior of NSCLC, underscoring its potential as a promising therapeutic target and prognostic marker. Full article

(This article belongs to the Section Cancer Therapy)

24 pages, 5341 KB

Open AccessArticle

Molecular Pathology of Advanced NSCLC: Biomarkers and Therapeutic Decisions

by Melanie Winter, Jan Jeroch, Maximilian Wetz, Marc-Alexander Rauschendorf and Peter J. Wild

Cancers 2026, 18(2), 216; https://doi.org/10.3390/cancers18020216 - 9 Jan 2026

Abstract

Background: Advances in molecular pathology have transformed NSCLC (Non-Small Cell Lung Cancer) diagnosis, prognosis, and treatment by enabling precise tumor characterization and targeted therapeutic strategies. We review key genomic alterations in NSCLC, including EGFR (epidermal growth factor receptor) mutations, ALK (anaplastic lymphoma kinase) [...] Read more.

Background: Advances in molecular pathology have transformed NSCLC (Non-Small Cell Lung Cancer) diagnosis, prognosis, and treatment by enabling precise tumor characterization and targeted therapeutic strategies. We review key genomic alterations in NSCLC, including EGFR (epidermal growth factor receptor) mutations, ALK (anaplastic lymphoma kinase) and ROS1 (ROS proto-oncogene 1) rearrangements, BRAF (B-Raf proto-oncogene serine/threonine kinase) mutations, MET (mesenchymal–epithelial transition factor) alterations, KRAS (Kirsten rat sarcoma) mutations, HER2 (human epidermal growth factor receptor 2) alterations and emerging NTRK (neurotrophic receptor tyrosine kinase) fusions and AXL-related pathways. Methods: A total of 48 patients with NSCLC was analyzed, including 22 women and 26 men (mean age 70 years, range 44–86). Tumor specimens were classified histologically as adenocarcinomas (n = 81%) or squamous cell carcinomas (n = 19%). Smoking history, PD-L1 (programmed death-ligand 1) expression, and genetic alterations were assessed. NGS (Next-generation sequencing) identified genomic variants, which were classified according to ACMG (American College of Medical Genetics and Genomics) guidelines. Results: The cohort consisted of 29 former smokers, 13 current smokers, and 5 non-smokers (12%), with a mean smoking burden of 33 pack years. PD-L1 TPS (tumor proportion score) was ≥50% in 10 patients, ≥1–<50% in 22, and <1% in 15 patients. In total, 120 genomic variants were detected (allele frequency ≥ 5%). Of these, 52 (43%) were classified as likely pathogenic or pathogenic, 48 (40%) as variants of unknown significance, and 20 (17%) as benign or likely benign. The most frequently altered genes were TP53 (tumor protein p53) (31%), KRAS and EGFR (15% each), and STK11 (serine/threonine kinase 11) (12%). Adenocarcinomas accounted for 89% of all alterations, with TP53 (21%) and KRAS (15%) being most common, while squamous cell carcinomas predominantly harbored TP53 (38%) and MET (15%) mutations. In patients with PD-L1 TPS ≥ 50%, KRAS mutations were enriched (50%), particularly KRAS G12C and G12D, with frequent co-occurrence of TP53 mutations (20%). No pathogenic EGFR mutations were detected in this subgroup. Conclusions: Comprehensive genomic profiling in NSCLC revealed a high prevalence of clinically relevant mutations, with TP53, KRAS and EGFR as the dominant drivers. The strong association of KRAS mutations with high PD-L1 expression, irrespective of smoking history, highlights the interplay between genetic and immunological pathways in NSCLC. These findings support the routine implementation of broad molecular testing to guide precision oncology approaches in both adenocarcinoma and squamous cell carcinoma patients. Full article

(This article belongs to the Section Cancer Pathophysiology)

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