Cancer Science最新文献

{"title":"WDR12 Promotes Glucose Metabolism via PFKFB4 Upregulation in Gastric Cancer.","authors":"Rutong Zhang, Dehua Liu, Xiaoxi Feng, Aoxing Cheng, Zhenye Yang, Kaiguang Zhang","doi":"10.1111/cas.70513","DOIUrl":"10.1111/cas.70513","url":null,"abstract":"<p><p>Metabolic reprogramming is a hallmark of gastric cancer (GC); however, the role of transcriptional regulators in modulating glycolysis remains incompletely understood. By integrating proteomic, transcriptomic, and CRISPR-based functional screening datasets, we identified WDR12, a WD40-family protein that is upregulated in GC and associated with poor patient survival. WDR12 silencing suppressed GC cell proliferation and tumor growth in vitro and in vivo and markedly reduced glycolytic flux. Mechanistically, WDR12 interacts with TDP43 and promotes its occupancy at the PFKFB4 promoter, thereby increasing PFKFB4 transcription. Restoration of PFKFB4 expression partially rescued the metabolic and proliferative defects caused by WDR12 knockdown. Together, these findings implicate WDR12 in GC metabolic reprogramming and suggest a potential metabolic vulnerability associated with WDR12-dependent regulation of PFKFB4 through TDP43.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-Derived Immune Gene Signature Predicts Prognosis and Therapeutic Vulnerabilities in Multiple Myeloma.","authors":"Kai Wang, Chenfei Zhao, Jingru Shi, Shiwei Liu, Yi Chen, Jujuan Wang, Zhengxu Sun, Sanmei Wang, Lei Fan, Jin Fan, Xiaoyan Qu","doi":"10.1111/cas.70523","DOIUrl":"10.1111/cas.70523","url":null,"abstract":"<p><p>The immune microenvironment contributes substantially to the biological and clinical heterogeneity of multiple myeloma (MM), yet immune-related molecular biomarkers with reproducible prognostic value remain limited. Here, we developed a 12-gene immune-related gene signature (IRGS) using an integrative machine-learning framework and evaluated its prognostic performance across multiple MM cohorts. The IRGS consistently stratified overall survival and remained independently associated with outcome after adjustment for established clinical covariates. Its prognostic discrimination was comparable to that of IFM15 and generally exceeded that of MRCIX6 and a mitophagy-related signature across the evaluated validation datasets. Single-cell RNA sequencing further revealed marked cell type-dependent variation in the activity of the 12-gene module, with comparatively low activity in plasma cells and higher activity in several non-plasma compartments, indicating that the bulk-derived IRGS reflects a multicellular bone marrow transcriptional context rather than an exclusively malignant plasma cell intrinsic program. Somatic mutation analysis identified distinct mutational patterns between IRGS-defined groups, including relative enrichment of DIS3 mutations in the low-IRGS group and MUC16 mutations in the high-IRGS group, together with a modestly higher tumor mutational burden in low-IRGS patients. Transcriptome-based drug-response prediction further suggested differential therapeutic vulnerabilities, with high- and low-IRGS groups showing distinct predicted sensitivity patterns across apoptosis-, DNA damage-, BET-, checkpoint-, and replication-stress-related agents. Collectively, these findings define the IRGS as a complementary immune-associated molecular biomarker for prognostic stratification in MM and provide a framework linking prognosis with multicellular transcriptional context, somatic mutational characteristics, and candidate therapeutic vulnerabilities.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment-Free Remission in Chronic Myeloid Leukemia: Toward Precision and Personalized Approaches to Functional Cure.","authors":"Hiroshi Ureshino, Shinya Kimura","doi":"10.1111/cas.70532","DOIUrl":"10.1111/cas.70532","url":null,"abstract":"<p><p>Treatment-free remission (TFR), defined as the maintenance of molecular remission without resumption of therapy after tyrosine kinase inhibitor (TKI) discontinuation, represents the clinical manifestation of functional cure in chronic-phase chronic myeloid leukemia (CML-CP), in which durable disease control is maintained without ongoing therapy despite the potential persistence of residual leukemic stem cells (LSCs). Emerging evidence supports a model in which outcomes after TKI discontinuation are determined by the balance between residual LSC persistence and coordinated host immune surveillance. Natural killer (NK)-cell abundance and maturation have shown the most consistent associations with TFR, while killer immunoglobulin-like receptor (KIR)-human leukocyte antigen (HLA) immunogenetics may further influence NK-cell education and antileukemic activity. Adaptive and regulatory mechanisms-including leukemia-associated antigen-specific cytotoxic T lymphocytes, T-cell receptor repertoire dynamics, T-cell exhaustion, plasmacytoid dendritic cells, and regulatory T cells-are increasingly implicated in residual disease control. Neutrophil abundance and maturation have also emerged as readily accessible candidate biomarkers. In parallel, persistent LSCs exploit BCR::ABL1-independent survival programs, immune-evasion mechanisms, and the protective bone marrow niche, providing a reservoir for molecular relapse. These observations argue against reliance on any single biomarker and instead support integrated models incorporating clinical variables, molecular residual disease, immune competence, immunogenetics, and LSC biology. Most candidate biomarkers remain exploratory and require independent prospective validation. Such multidimensional approaches may enable a transition from empiric TKI discontinuation toward precision, biomarker-guided TFR and extend durable functional cure to a broader population of patients with CML. Trail Registration: N/A.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Losartan Enhances Radiosensitivity by Reversing Immunosuppressive Tumor Microenvironment Induced by Radiotherapy in TNBC\".","authors":"","doi":"10.1111/cas.70528","DOIUrl":"10.1111/cas.70528","url":null,"abstract":"","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of DVDMS-Photodynamic Therapy for Dysphagia in Advanced Esophageal Cancer: A Phase II Clinical Trial.","authors":"Jun Zhou, Shegan Gao, Jiajia Yuan, Hao Chen, Yongqian Shu, Huizhen Fan, Yanshuo Cao, Tanyou Shan, Caihong Dong, Hao Zhang, Qingting Song, Baobao Xin, Hao Zhang, Zhihao Lu, Lin Shen","doi":"10.1111/cas.70507","DOIUrl":"10.1111/cas.70507","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) is a localized treatment for esophageal stenosis and dysphagia in advanced cancer. This study evaluated the efficacy and safety of Cosiporfin sodium (DVDMS)-mediated PDT for dysphagia in advanced esophageal cancer. In this Phase II trial, patients with advanced esophageal cancer and Grade ≥ 2 dysphagia, who were unsuitable for or declined curative therapies, received 0.2 mg/kg DVDMS followed by PDT (wavelength: 630 nm) at varying regimens: 102 J/cm (24 h post-injection), 200 J/cm (24 h), and 150 J/cm (18 h). Safety was the primary endpoint. The study enrolled 20 patients in the 102 J/cm 24 h group, 6 in the 200 J/cm 24 h group, and 4 in the 150 J/cm 18 h group. Two patients experienced dose-limiting toxicities: One upper abdominal pain (16.7%) in the 200 J/cm 24 h group and one non-cardiac chest pain (25.0%) in the 150 J/cm 18 h group. Common adverse events included non-cardiac chest pain (10.0%) related to DVDMS and non-cardiac chest pain (20.0%) and anemia (20.0%) related to PDT. The photosensitivity test showed that by day 4, 66.7% of patients tested negative, improving to 86.7% by day 7, and all patients were negative by day 28. The esophageal overall response rate was 40.0% on day 28. The median duration of esophageal response and median OS for all patients were 4.86 months (95% CI: 1.51-5.32) and 9.51 months (95% CI: 5.45-NE), respectively. DVDMS-mediated PDT demonstrates acceptable safety and sustained efficacy in improving esophageal stenosis and dysphagia in advanced esophageal cancer. Trial Registration: chictr.org.cn ChiCTR2000032829.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A CECT-Based 2PI System as a Novel Noninvasive Prognostic Tool for Hepatocellular Carcinoma: A Dual-Validation Study.","authors":"Yingzhu Cui, Dezhi Zhang, Fan Lin, Liang Guo, Lei Zhang, Kan He, Hongbin Wang, Shuang Zheng, Kun Zhang, Yu Fu, Huimao Zhang","doi":"10.1111/cas.70519","DOIUrl":"10.1111/cas.70519","url":null,"abstract":"<p><p>This study aimed to develop and validate machine learning (ML) models integrating clinical parameters and the 2PI system (Pathology and Prognosis-Informed Imaging System) for predicting postoperative recurrence risk in hepatocellular carcinoma (HCC). The multicenter retrospective study included 496 patients with solitary HCC (≤ 5 cm). Surgical resection (SR) patients from the primary center constituted the training set; radiofrequency ablation (RFA) patients from the same center formed the internal test set; and SR patients from other centers served as the external test set. In the training set, multivariable logistic regression identified seven imaging features associated with pathological markers, with odds ratios calculated as exp(β). Kendall's tau-b coefficient was used to indicate the strength of association between pathology and recurrence risk. A dual-information pathway 2PI system was constructed based on these coefficients, and the performance of ML models integrating clinical parameters and the 2PI system was evaluated. A total of 496 patients (mean age 58 ± 10 years, 376 men) were enrolled. Patients were stratified into high- and low-risk groups using a 2PI system threshold of ≥ 19. The Random Survival Forest (RSF) model incorporating clinical parameters and the 2PI system demonstrated favorable predictive performance across all sets (training: C-index 0.76 [95% CI: 0.72-0.80]; internal test: C-index 0.69 [95% CI: 0.63-0.75]; external test: C-index 0.68 [95% CI: 0.57-0.79]). The 2PI system applies a joint weighting strategy to create a straightforward image scoring system that enhances postoperative recurrence risk prediction for solitary HCC, demonstrating preliminary generalizability across both SR and RFA cohorts.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Long Noncoding RNA OVAAL Enhances Nucleotide Synthesis Through Pyruvate Carboxylase to Promote 5-Fluorouracil Resistance in Gastric Cancer\".","authors":"","doi":"10.1111/cas.70529","DOIUrl":"10.1111/cas.70529","url":null,"abstract":"","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triggering SORL1 Expression Restricts ccRCC Progression by Inducing Ubiquitination-Mediated c-Myc Degradation.","authors":"Keyi Wang, Wei Song, Qi Bai, Shaoze Shen, Xiao Lu, Chenxuan Su, Shi Yang, Yidi Wang, Yu Xia, Rui Zan, Shuai Jiang, Jianming Guo","doi":"10.1111/cas.70516","DOIUrl":"10.1111/cas.70516","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) represents one of the most prevalent malignancies worldwide, characterized by high incidence and mortality rates. It is characterized by mitochondrial dysfunction with enhanced Warburg effect. In this study, we identify the sortilin-related receptor 1 (SORL1) as a regulator of ccRCC progression and a potential molecular target for oxidative phosphorylation inhibition. The present evidence demonstrates that SORL1 promotes the ubiquitin-mediated degradation of C-MYC via TRIM22, which is associated with the downregulation of ACO2 and IDH2 and a consequent suppression of oxidative phosphorylation capacity. Molecular investigations further indicated that Cefoperazone could bind to SORL1 and increase its protein level, exerting the SORL1-triggering function. Targeting delivery Cefoperazone exhibits unexpected anti-tumor performances in ccRCC. Collectively, our findings establish SORL1 as a tumor suppressor in ccRCC and highlight its potential as a therapeutic target in advancing ccRCC clinical treatment strategies.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Musashi-1 Drives Radioresistance and Stemness in Head and Neck Squamous Cell Carcinoma via a Radioresistant FaDu Model.","authors":"Na-Eun Kang, Chan-Woong Jung, Yun-Ju Kim, Sung-Gil Chi, Jeong-Yub Kim, Myung-Jin Park","doi":"10.1111/cas.70521","DOIUrl":"10.1111/cas.70521","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is frequently managed with radiotherapy, but the emergence of radioresistant cancer cells with cancer stem cell (CSC) properties remains a major clinical obstacle. Here, we established a radioresistant FaDu cell line (F-IRR) by repeated fractionated irradiation to investigate the molecular basis of radiation resistance in HNSCC. Irradiated colony-forming assays confirmed the radioresistant phenotype of F-IRR cells. Although F-IRR cells proliferated more slowly than parental cells, they exhibited markedly enhanced CSC activity, as demonstrated by sphere formation, limiting dilution, and soft agar assays. Among multiple stem cell-associated markers, Musashi-1 (MSI1)-an ribonucleic acid (RNA)-binding protein with established roles in CSC maintenance-was the most prominently upregulated, as confirmed by western blot, reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry. Functional studies demonstrated that siRNA-mediated knockdown of MSI1 suppressed stemness and radioresistance in F-IRR cells, whereas stable MSI1 overexpression in parental FaDu and CAL27 cells conferred enhanced stemness and radiation resistance. RNA sequencing and pathway analysis identified hyperactivation of the mitogen-activated protein kinase (MAPK) pathway in F-IRR cells, and targeted inhibition experiments showed that the c-Jun N-terminal kinase (JNK) signaling pathway was the primary upstream regulator of MSI1 expression. JNK inhibition with SP600125 reduced MSI1 levels and attenuated stemness and radioresistance in F-IRR cells. In vivo xenograft experiments further confirmed that F-IRR cells possessed greater tumorigenic potential and radioresistance than parental cells, with high expression of MSI1 and phospho-JNK in tumor tissues. Collectively, these findings identify the JNK-MSI1 axis as a critical driver of CSC-mediated radioresistance in HNSCC and a promising therapeutic target for overcoming treatment failure.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-Informed Whole-Animal Kinome Screening Reveals Shared Kinase Vulnerabilities Across Driver Contexts in PDAC.","authors":"Han Hai, Takako Ooshio, Hui Jiang, Taku Kimura, Yusuke Satoh, Soichiro Hata, Taiga Hirata, Jiayi Liu, Tongwei Liu, Ryodai Yamamura, Masahiro Sonoshita","doi":"10.1111/cas.70522","DOIUrl":"10.1111/cas.70522","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) frequently harbors co-occurring alterations in KRAS, TP53, CDKN2A, and SMAD4, yet how clinically prevalent driver combinations shape kinase dependencies remains incompletely understood. To systematically interrogate genotype-dependent and shared vulnerabilities, we generated Drosophila models representing dominant PDAC driver contexts, including 2-hit (KRAS-TP53) and 3-hit (KRAS-TP53-CDKN2A or KRAS-TP53-SMAD4) genotypes, and conducted comparative whole-animal genetic screening using organismal viability as a phenotypic readout. This approach identified both genotype-specific modifiers and a subset of kinases whose suppression consistently improved viability across distinct genetic contexts, enabling prioritization of conserved candidates for cross-species validation. Among these, the Drosophila kinase Drak, orthologous to human STK17A/STK17B, emerged as a recurrent shared vulnerability. Functional validation in three-dimensional spheroid cultures of human PDAC cell lines representing distinct driver genotypes demonstrated that STK17B perturbation impairs spheroid growth across models. Transcriptomic profiling further revealed coordinated downregulation of gene sets linked to DNA replication and E2F-driven cell-cycle programs upon STK17B knockdown. Together, these findings establish a genotype-informed screening framework for systematic discovery of shared and context-dependent kinase dependencies in PDAC, and nominate STK17B as a conserved genetic vulnerability across dominant driver contexts.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}