Journal of Cancer Research and Clinical Oncology最新文献

{"title":"The influence of urban versus rural residence and travel distance on net income, out-of-pocket payments and quality of life in German head and neck cancer survivors.","authors":"Jonas Rast, Theresa Wald, Veit Zebralla, Andreas Dietz, Gunnar Wichmann, Susanne Wiegand","doi":"10.1007/s00432-026-06534-5","DOIUrl":"10.1007/s00432-026-06534-5","url":null,"abstract":"<p><strong>Purpose: </strong>German HNC survivors frequently experience substantial financial burden (FB). Geographic distance to cancer care centers (CCC) may increase FB negatively affecting QoL and outcome by creating barriers to diagnosis, treatment, and aftercare. We evaluated the impact of distance to CCC on FB and provide insights into socioeconomic conditions of HNC patients.</p><p><strong>Methods: </strong>Between August 2022 and March 2023, 200 HNC patients completed a comprehensive questionnaire assessing financial aspects, including self-reported FB, and the EORTC QLQ-C30. Distances from each patient's residence to the treating CCC were recorded and analyzed in relation to socioeconomic characteristics. Parametric and non-parametric statistical methods were applied to assess subgroup differences associated with travel distance.</p><p><strong>Results: </strong>The mean travel distance was 27.9 km (95% CI 20.3-35.5). Patients residing in rural areas and farther from aftercare centers reported significantly higher out-of-pocket payments due to travel expenses and additional costs. A significant income disparity was observed between HNC patients living in urban cores and the general population within the same ZIP code (Δ - 499.56€; p = 0.014). Rural patients reported significantly higher financial difficulty scores on the EORTC QLQ-C30, reflecting greater FB and impaired QoL (p < 0.001). Overall, HNC survivors had significantly lower income than the general population, with the lowest levels observed among urban patients.</p><p><strong>Conclusion: </strong>Increased distance to CCC is associated with higher FB and reduced QoL among HNC survivors, even in a statutory healthcare system. These disparities highlight the need for targeted interventions to reduce financial toxicity and improve access to cancer aftercare.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The human trophoblast cell-surface antigen 2 (TROP-2) expression on metastasized breast cancer.","authors":"M Weich, L Christl, M Kiesel, J Salmen, A Wöckel, J Diessner, E Gerhard-Hartmann, T Schlaiss","doi":"10.1007/s00432-026-06551-4","DOIUrl":"10.1007/s00432-026-06551-4","url":null,"abstract":"<p><strong>Purpose: </strong>The antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and datopotamab deruxtecan target trophoblast cell surface antigen 2 (TROP-2) and have shown significant efficacy in HER2-negative metastatic breast cancer (mBC). As TROP-2 may serve as a target across multiple treatment lines, detailed information on TROP-2 expression over time is of great interest.</p><p><strong>Methods: </strong>TROP-2 expression was analyzed in breast cancer (BC) samples from patients treated at the University Hospital Würzburg between 2004 and 2025 at clinically indicated biopsy time points (TP), and, in a subset, before and after SG treatment. Expression was assessed immunohistochemically using the H-score (range 0-300).</p><p><strong>Results: </strong>We evaluated 229 samples from 76 patients. Overall, patient-level TROP-2 expression was high (mean H-score 241.3 ± 73.2) and largely stable over time (TP1: 235.7 ± 60.8, n = 76; TP2: 244.6 ± 77.4, n = 72; TP3: 245.3 ± 84.4, n = 39; TP4: 244.9 ± 95.6, n = 8). However, 21 patients exhibited a decline in TROP-2 expression during disease progression, defined as a decrease of ≥ 50 H-score points between two consecutive TPs. Among 13 patients with paired biopsies obtained pre- and post-SG treatment, the mean TROP-2 H-score decreased from 227.0 ± 74.6 before SG to 202.9 ± 99.4 after SG (mean change - 24.1 ± 86.0; median 1.7, range - 170 to 110; Wilcoxon p = 0.542). TROP-2 H-score decreased in 6/13 patients and increased in 7/13 patients. Exploratory PFS analysis showed no statistically significant difference by post-SG TROP-2 change (log-rank p = 0.526).</p><p><strong>Conclusion: </strong>TROP-2 expression was generally high and relatively stable; however, some patients showed declining levels over time.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 7","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timosaponin AIII-based liposomes loaded with Auranofin for the induction of ferroptosis in anaplastic thyroid carcinoma.","authors":"Xinyi Deng, Lei Yang, Dihua Li, Yan Wang, Qiang Jia, Ning Li, Zhaowei Meng","doi":"10.1007/s00432-026-06538-1","DOIUrl":"10.1007/s00432-026-06538-1","url":null,"abstract":"<p><strong>Purpose: </strong>Anaplastic thyroid carcinoma (ATC) is an exceptionally aggressive malignancy that, despite accounting for only 1%-1.5% of all thyroid cancers, is responsible for over half of thyroid cancer-related deaths. Characterized by limited treatment options and a poor prognosis, ATC presents a critical clinical challenge. In this study, we developed and evaluated an innovative liposomal system (T-AUF-LPs) co-loading Auranofin (AUF) and Timosaponin AIII (TAIII) aimed at inducing ferroptosis in ATC cells.</p><p><strong>Methods: </strong>T-AUF-LPs were prepared via the film-hydration method and their physicochemical properties were characterized. Cellular uptake, anti-proliferative effects, and ferroptosis-related mechanisms-including reactive oxygen species (ROS), iron levels, glutathione (GSH), GPX4, ACSL4, and NCOA4-were assessed in CAL-62 and 8505C ATC cell lines. In vivo antitumor efficacy and biosafety were evaluated using a BALB/c nude mouse xenograft model.</p><p><strong>Results: </strong>T-AUF-LPs showed superior physicochemical properties compared to conventional liposomes, including uniform spherical morphology, reduced particle size, and enhanced encapsulation efficiency. Cellular assays revealed significantly improved uptake of T-AUF-LPs in both ATC cell lines. The formulation inhibited cell proliferation in a dose-dependent manner, an effect effectively reversed by ferrostatin-1, confirming ferroptosis as the primary cell death mechanism. Mechanistic investigations indicated that T-AUF-LPs treatment increased intracellular ROS and iron levels, depleted GSH, and induced upregulation of ACSL4 and NCOA4 along with downregulation of GPX4. In vivo evaluation demonstrated effective tumor growth suppression with an excellent safety profile and no significant organ toxicity.</p><p><strong>Conclusion: </strong>T-AUF-LPs exert potent anti-tumor effects by inducing ferroptosis without causing systemic organ toxicity. They represent a promising therapeutic strategy for ATC, thereby addressing a critical unmet need in the management of this disease.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of CDDO‑TFEA on non‑small cell lung cancer growth, apoptosis, and stemness via the MEK/ERK pathway.","authors":"Jui-Ying Lee, Chia-Li Chung, Tzu-Ting Tseng, Shih-Hsun Kuo, Yu-Peng Liu, Ming-Tsang Wu, Hung-Pei Tsai, Aij-Lie Kwan","doi":"10.1007/s00432-026-06544-3","DOIUrl":"10.1007/s00432-026-06544-3","url":null,"abstract":"<p><strong>Purpose: </strong>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, and therapeutic resistance limits durable responses. We investigated the antitumor activity of CDDO-TFEA, a synthetic trifluoroethyl amide derivative of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, in NSCLC models.</p><p><strong>Methods: </strong>A549 and H1299 cells were treated with CDDO-TFEA and evaluated using MTT assays, Annexin V/7-aminoactinomycin D flow cytometry, tumorsphere and tube-formation assays, immunoblotting, and A549 xenograft experiments.</p><p><strong>Results: </strong>CDDO-TFEA decreased cell viability in a dose-dependent manner and induced apoptosis, as indicated by increased Annexin V positivity, PARP cleavage, cleaved caspase-3 expression, and TUNEL positivity. At 200 nM, CDDO-TFEA significantly suppressed tumorsphere formation in both cell lines and reduced CD133, octamer-binding transcription factor 4, SRY-box transcription factor 2, and vascular endothelial growth factor expression. Because only A549 cells formed tube-like networks, angiogenesis-related phenotypes were evaluated in A549 cells and were markedly inhibited by CDDO-TFEA. Mechanistically, CDDO-TFEA increased extracellular signal-regulated kinase phosphorylation, whereas MEK inhibition by U0126 or trametinib partially attenuated CDDO-TFEA-induced apoptosis and the suppression of tumorsphere formation, tube-like network formation, and stemness- and angiogenesis-related marker expression. In vivo, systemic CDDO-TFEA administration dose-dependently inhibited xenograft tumor growth.</p><p><strong>Conclusion: </strong>CDDO-TFEA exerts antitumor activity in NSCLC by inducing apoptosis and suppressing stemness-associated and angiogenesis-related phenotypes, partly through mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling. These findings support further preclinical development of CDDO-TFEA in NSCLC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: \"The status and determinants of demoralization in patients with colorectal cancer: a cross-sectional study in China\".","authors":"Kunyu Han, Jiahe Wang, Jiumao Lin","doi":"10.1007/s00432-026-06558-x","DOIUrl":"10.1007/s00432-026-06558-x","url":null,"abstract":"<p><p>Zhou et al. investigated demoralization syndrome (DS) among Chinese patients with colorectal cancer and identified cancer metastasis, anxiety, and depression as factors independently associated with greater DS severity. Their study provides valuable evidence for psychological screening and supportive care in this population. In this comment, we highlight two analytical considerations that may further strengthen the interpretation of their findings. First, although social support was associated with DS severity in univariate analysis, the loss of statistical significance after multivariable adjustment should not be interpreted as evidence of irrelevance; rather, social support may influence DS indirectly through anxiety, depression, or disease burden. Mediation or path analysis may therefore better reflect the underlying causal structure. Second, dichotomizing the continuous DS-II score into mild versus moderate-to-severe categories may reduce statistical power and obscure clinically meaningful variation. Analyzing the DS-II score as a continuous or ordinal outcome could provide a more informative assessment of the determinants of DS.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"152 7","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of patients with epithelioid hemangioendothelioma (EHE): a retrospective analysis of the Charité- Universitätsmedizin Berlin.","authors":"Jana K Striefler, F Brandes, A Strönisch, M Schmiester, A Dörr, L E Heil Olaizola, J Benckert, J Ihlow, A Jarosch, M Stiller, M von Laffert, S Roohani, D Kaul, R Öllinger, S Wittenberg, D Rau, S Märdian, F Tacke, L Bullinger, A Flörcken","doi":"10.1007/s00432-026-06549-y","DOIUrl":"10.1007/s00432-026-06549-y","url":null,"abstract":"<p><strong>Background: </strong>Epithelioid hemangioendothelioma (EHE) represents an extremely uncommon vascular sarcoma subentity. The clinical characteristics vary from low grade localized to high grade systemic disease and treatment ranges from active surveillance versus intensive therapeutic strategies. Due to its rarity, a standardized clinical management including an appropriate therapeutic approach has not yet been defined.</p><p><strong>Methods: </strong>Patients with EHE presenting at the Charité-Universitätsmedizin Berlin between 1997 and 2022 were included in the analysis. A retrospective database was established comprising demographic specifications, treatment, pathological features (including TFE3 expression level) and prognosis. Our single-centre data was then compared to previously published cohorts.</p><p><strong>Results: </strong>The cohort included n = 41 patients, with n = 16 men (39%) and n = 25 women (61%) with a median age of 53 years (range 20-88). The patients had limited comorbidities (median Charlson Comorbidity Index, CCI: 3) and a good performance status (median ECOG: 1). Median overall survival was not reached, with only n = 3 patients (7%) showing an aggressive course of disease (progression-free survival (PFS) ≤ 28 days). Isolated liver involvement was the predominant clinical presentation, observed in n = 26 patients (63%). At initial diagnosis, n = 17 (41%) patients showed systemic symptoms (e.g. anemia, weight loss) and n = 12 (29%) already had metastatic disease. Surgery was performed for therapeutic and/or diagnostic purposes in n = 20 (49%) patients, whereas only n = 5 (12%) received chemotherapy. In n = 2 of the latter, disease stabilization was achieved. Liver transplantation was performed in n = 5 (12%) patients and was associated with persisting disease-free survival. Molecular genetic data was retrieved in n = 21 (51%) patients regarding WWTR1-CAMTA1 fusion, and in n = 18 (44%) patients regarding TFE3 positivity. In 67% of analyzed samples, CAMTA1 fusion was found. In contrast, TFE3 expression was observed in 22% only. Both CAMTA1 fusion and TFE3 positivity were observed in n = 3 patients (18%).</p><p><strong>Conclusions: </strong>This analysis of EHE patients treated at Charité-Universitätsmedizin Berlin mirrors published cohorts regarding clinical behavior and OS. The observed clinical heterogeneity underlines the necessity for personalized therapeutic strategies in this rare disease. Molecular characterization is increasingly recognized as a component of contemporary clinical care, as it may identify molecular subclasses associated with aggressive disease and guide management strategies in the future. Moreover, standardized molecular profiling also enables evaluation of patient eligibility for clinical trials.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the potential role of miR-124 in angiogenesis in colorectal cancer.","authors":"Ali Ahmadizad Firouzjaei, Kazem Sharifi, Samira Mohammadi-Yeganeh, Seyed Hamid Aghaee-Bakhtiari","doi":"10.1007/s00432-026-06550-5","DOIUrl":"10.1007/s00432-026-06550-5","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a significant contributor to cancer-associated mortality globally, emphasizing the urgent requirement for effective therapeutic strategies. Angiogenesis, a key process in CRC progression, has garnered attention as a target for anti-cancer therapies. microRNAs (miRNAs) have emerged as potential regulators of angiogenesis in cancer, including CRC. The goal of this investigation was to discover miRNAs that regulate angiogenesis in CRC and assess the impact of selected miRNA on CRC cells.</p><p><strong>Methods: </strong>Through an in-silico analysis of angiogenesis-related genes (ARGs), we identified miRNAs with concurrent targeting of key genes involved in CRC angiogenesis, employing bioinformatic databases. Subsequently, the suppressive impacts of overexpressed miRNA on the expression of target genes were confirmed using quantitative real-time PCR. To evaluate angiogenesis, chicken chorioallantoic membrane (CAM) assays were employed.</p><p><strong>Results: </strong>Our computational study identified hsa-miR-124-3p, hsa-miR-16-5p, hsa-miR-1-3p, hsa-miR-101-3p, and hsa-miR-146a-5p as possible angiogenesis modulators in CRC. Among these, hsa-miR-124-3p targeted the greatest number of genes. In CRC cells, miR-124 overexpression reduced mRNA levels of ANGPT2, HIF1A, MMP9, and VEGFA genes. Furthermore, it was discovered that upregulation of miR-124 can inhibit vascularization of the CAM.</p><p><strong>Conclusion: </strong>These observations imply that miR-124 offers prospects as a potential therapy for CRC treatment. Further investigations are warranted to ascertain the therapeutic potential of miR-124-3p in animal models and patient samples. Our investigation underscores the significance of miRNAs as therapeutic targets for cancer angiogenesis and preliminary highlights the potential of miR‑124‑3p-mediated pathways as candidates for targeted intervention in CRC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell hdWGCNA identifies checkpoint inhibitor pneumonitis-linked CD4 + T-cell subsets driving immunotherapy response and prognosis in lung cancer.","authors":"Qiuming Chen, Shaocong Mo, Jun Cheng, Linhai Zhu","doi":"10.1007/s00432-026-06522-9","DOIUrl":"10.1007/s00432-026-06522-9","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have achieved promising efficacy in lung cancer patients, yet checkpoint inhibitor-related pneumonitis (CIP) remains a severe and incompletely understood complication. The pathogenesis of CIP and its impact on immunotherapy outcomes remain elusive, especially the role of specific immune cell subsets in mediating these processes.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) data from CIP patients were analyzed to delineate the distinct immune microenvironment landscape. High-dimensional weighted gene co-expression network analysis (hdWGCNA) was performed to identify CIP-related CD4 + T cell gene modules. Key results were validated in an independent lung adenocarcinoma (LUAD) cohort, and a prognostic signature was constructed. Immunofluorescence staining was applied to verify the existence of the identified T-cell subsets in CIP-lung tissues.</p><p><strong>Results: </strong>Our analysis uncovered prominent CD4 + T cell infiltration in the CIP immune microenvironment. hdWGCNA identified key CIP-associated CD4 + T cell genes enriched in pathways including viral response, cytokine production and T cell differentiation. Validation in the LUAD cohort verified robust associations between these CD4 + T cell subsets and both patient prognosis and immunotherapy response. The constructed prognostic signature exhibited favorable predictive performance, with BIRC3 identified as the leading risk gene. Immunofluorescence staining confirmed the spatial localization of BIRC3 + CD4+ T cells in CIP patients.</p><p><strong>Conclusion: </strong>This study identifies critical CD4 + T cell subpopulations mediating CIP pathogenesis and establishes a robust gene signature for predicting survival and ICI response in LUAD patients. Our findings provide mechanistic insights into CIP progression and offer potential therapeutic targets for the clinical management of this life-threatening immunotherapy complication.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFE3-rearranged PEComa with hepatic and pulmonary involvement: diagnostic challenges and resistance to mTOR-targeted therapy.","authors":"Sally Chahine, Tasnim Diab, Maria El Tannir, Ghassan Farhat, Nawaf Jurdi, Hazem I Assi","doi":"10.1007/s00432-026-06556-z","DOIUrl":"10.1007/s00432-026-06556-z","url":null,"abstract":"<p><strong>Background: </strong>Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms composed of epithelioid cells that co-express melanocytic and smooth muscle markers. They can arise in various anatomic sites, most commonly the uterus, retroperitoneum, gastrointestinal tract, and liver. While most PEComas are sporadic and associated with TSC1/TSC2 mutations leading to mTOR pathway activation, a distinct molecular subset harbors TFE3 gene rearrangements, often exhibiting more aggressive clinical behavior. Given their rarity, the diagnosis and management of PEComas remain challenging and largely unstandardized.</p><p><strong>Case presentation: </strong>We report the case of a 37-year-old woman with no significant medical history who presented with fatigue, unintentional weight loss, and vomiting. Imaging revealed a large hepatic mass and pulmonary nodules. Histopathological and immunohistochemical evaluation confirmed a diagnosis of TFE3-rearranged PEComa involving the liver and left upper lung lobe. The patient underwent right partial hepatectomy with complete resection of the hepatic lesion. Subsequent disease progression was noted in the lung, lymph nodes, and bone despite treatment with an mTOR inhibitor.</p><p><strong>Conclusion: </strong>TFE3-rearranged PEComas represent a rare and aggressive molecular subset with limited therapeutic options. This case demonstrates resistance to mTOR inhibition, highlighting the critical importance of molecular subtyping to distinguish TFE3-rearranged from TSC1/TSC2-mutant disease and guide individualized management. Expanded molecular profiling is essential to refine treatment strategies for this uncommon entity.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GALNT5 drives colorectal cancer progression and chemoresistance via PI3K/Akt/ABCC1 axis.","authors":"Qiong Wu, Liehao Yang, Bing Bai, Jian Jiang, Tong Liu, Yiquan Sun, Changmiao Wang","doi":"10.1007/s00432-026-06533-6","DOIUrl":"10.1007/s00432-026-06533-6","url":null,"abstract":"<p><strong>Background: </strong>Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), a member of the GALNT enzyme family, has been implicated in the pathogenesis of various malignancies. However, its precise role in colorectal cancer (CRC) progression and its contribution to acquired resistance to the FOLFOX components (oxaliplatin and 5-fluorouracil) remains poorly understood. This study aimed to elucidate the biological functions of GALNT5 in CRC pathogenesis and chemoresistance.</p><p><strong>Methods: </strong>GALNT5 expression in CRC cell lines was evaluated through integrated bioinformatics analyses, RNA sequencing (RNA-Seq), RT-qPCR, and Western blotting. Isogenic CRC sublines resistant to oxaliplatin (LoVo/L) or 5-fluorouracil (LoVo/5FU) were established separately by chronic exposure to each drug. RNA-Seq was employed to identify downstream signaling pathways and effector genes modulated by GALNT5. VVL lectin pull-down assays were performed to confirm that GALNT5 mediates O-GalNAc glycosylation of EGFR-an upstream activator of the PI3K/Akt signaling pathway. Functional assays, including CCK-8 and Transwell, were conducted to assess cell proliferation, apoptosis, and invasion. The involvement of the PI3K pathway was examined using the PI3K agonist 740Y-P, while expression changes of the downstream effector ABCC1 were analyzed both in vitro and in vivo.</p><p><strong>Results: </strong>GALNT5 was significantly upregulated in CRC cell lines compared to the normal colonic epithelial cell line NCM460. Knockdown of GALNT5 markedly suppressed proliferation and invasion, while promoting apoptosis in both parental and chemoresistant CRC cells. Silencing GALNT5 enhanced the sensitivity of resistant cells to oxaliplatin (L-OHP) and 5-fluorouracil (5FU), an effect that was reversible upon PI3K pathway activation, indicating the involvement of the PI3K/Akt axis. Mechanistically, GALNT5 activated the PI3K/Akt axis through O-GalNAc glycosylation of EGFR. Furthermore, GALNT5 depletion led to downregulation of the multidrug resistance-associated protein ABCC1 in vitro and in vivo.</p><p><strong>Conclusion: </strong>GALNT5 facilitates malignant progression in CRC by promoting O-GalNAc glycosylation of EGFR and thereby activating the PI3K/Akt pathway, and confers resistance to L-OHP and 5FU through upregulation of ABCC1. These findings suggest GALNT5 as a potential diagnostic biomarker and a promising therapeutic target for overcoming chemoresistance in CRC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}