British Journal of Cancer最新文献

{"title":"Low-fat dietary pattern and dietary advanced glycation end-products intake: a secondary analysis of the Women’s Health Initiative randomized trial","authors":"Margaret S. Pichardo, Rebecca P. Hunt, Lindsay L. Peterson, Kathy Pan, Mace Coday, Su Yon Jung, Linda Snetselaar, Marian L. Neuhouser, Susan E. Steck, Fred K. Tabung, Nazmus Saquib, JoAnn E. Manson, Rowan T. Chlebowski","doi":"10.1038/s41416-026-03514-x","DOIUrl":"10.1038/s41416-026-03514-x","url":null,"abstract":"In the Women’s Health Initiative (WHI) Dietary Modification (DM) randomized trial, a low-fat dietary pattern intervention reduced breast cancer mortality (P = 0.02). Higher dietary advanced glycation end-products (dAGE) may be associated with higher breast cancer incidence. In this report, we examined whether the WHI dietary intervention influenced dAGE consumption. Of 48,835 postmenopausal women randomized (40:60) to dietary intervention versus usual diet comparison, 40,209 had food frequency questionnaires at baseline, and serially through 5–7 years, which were used to estimate dAGE scores (kilo Unit/1000 kilocalories [kU/1000 kcal]) using a commonly referenced database. Multivariate regressions with repeated dAGE measures were examined by randomization group. Baseline mean dAGE scores were similar for intervention (7542 kU/1000 kcal, standard deviation (SD) = 912) and comparison (7514 kU/1000 kcal, SD = 917) groups. Through 5–7 years, dAGE scores were persistently lower in intervention versus comparison groups (mean range 5361–6236 kU/1000 kcal versus 7159–7669 kU/1000 kcal (P < 0.0001). The WHI low-fat dietary pattern intervention substantially reduced dAGE consumption. NCT00000611; Date: 10/28/1999.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1424-1429"},"PeriodicalIF":7.8,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13564117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomics differences of histopathological growth patterns in colorectal cancer liver metastases","authors":"Maria Escriva Conde, Axel Andersson, Peter Vermeulen, Mats Nilsson, Hanna Nyström","doi":"10.1038/s41416-026-03567-y","DOIUrl":"10.1038/s41416-026-03567-y","url":null,"abstract":"Histopathological growth patterns (HGPs) have emerged as prognostic and predictive biomarkers in colorectal liver metastases (CLM). The desmoplastic/encapsulating HGP (EHGP) is associated with improved survival after surgery, whereas the replacement HGP (RHGP) is associated with poorer outcomes. However, HGPs can only be reliably assessed postoperatively, limiting their use as preoperative biomarkers. A deeper molecular understanding of HGPs could inform biomarker development and therapeutic strategies, including approaches to promote EHGP. We applied in situ sequencing (ISS), an image-based spatial transcriptomics method, to map RNA expression in CLM tissue. Two custom gene panels (150 and 175 genes) were analysed in a chemonaïve cohort of resected CLM tissue from 19 patients with EHGP and RHGP. Distinct molecular programmes characterised the two patterns. RHGP was associated with damaged SAA1+ hepatocytes, KRT18+ neoplastic cells, and bifunctional hepatocyte-cholangiocyte cells. EHGP showed interferon-γ signalling, cytotoxic T-cell infiltration, and a fibrotic capsule with zonation-specific features: hepatic stellate cell activation, angiogenesis, and immune recruitment on the liver-facing side, and cancer-associated fibroblasts on the tumour-facing side. These differences imply that growth patterns emerge from tumour-host driven interactions. They reveal new molecular features of the metastatic niche. These insights may inform the search for novel treatment strategies.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1499-1511"},"PeriodicalIF":7.8,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03567-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clarifying causal and translational inference in studies of ambient PM2.5 and lung cancer","authors":"Man Sun, Dan Zang, Jun Chen","doi":"10.1038/s41416-026-03555-2","DOIUrl":"10.1038/s41416-026-03555-2","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 5","pages":"675-676"},"PeriodicalIF":7.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signatures of micropeptides encoded by lncRNAs in cancer progression and metastasis","authors":"Stav Zok, Michal Linial","doi":"10.1038/s41416-026-03556-1","DOIUrl":"10.1038/s41416-026-03556-1","url":null,"abstract":"Long non-coding RNAs (lncRNAs) regulate gene expression, chromatin organization, and cellular signaling. Although traditionally considered non-coding, 21% of the ~190,000 annotated lncRNA transcripts contain poorly characterized open reading frames with unknown function. We systematically identified lncRNAs encoding micropeptides (MPs) using integrated computational and experimental evidence. Expression profiles across 17 cancer types from The Cancer Genome Atlas (TCGA) were analyzed to identify cancer-associated and transitional lncRNAs (Tr-lncRNAs). Structural modeling using AlphaFold was further applied to predict folding. We identified 478 lncRNA genes encoding 1782 MPs (10–100 amino acids). These MPs exhibit distinct amino acid and dipeptide compositions and are enriched for specific 4-mer motifs compared with canonical proteins. A subset of lncRNAs, including TNN-AS1, PVT1, XIST, and SNHG family members, encode multiple MPs. Analysis across cancer stages identified 2399 Tr-lncRNAs, most of them were cancer type and stage specific. Among these, 314 highly confident MPs from 72 Tr-lncRNAs were further analyzed. Pan-cancer analysis suggested MP-like functions for Tr-lncRNAs such as LINC01234, HAND2-AS1, XIST, UCA1, and HOXA11-AS. While most MPs are predicted to be intrinsically disordered, 3D structural modeling revealed several MPs with stable folds, including ubiquitin-like and RNase H-like structures. Tr-lncRNA–derived MPs represent a previously underexplored class of potentially functional molecules associated with cancer clinical annotation and may serve as biomarkers for disease progression.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1390-1401"},"PeriodicalIF":7.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03556-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR4-associated APOBEC3 mutagenesis characterizes HER2-enriched subtype of human breast cancer","authors":"Ju-Yul Jeong, Chae-Yi Kim, A-Reum Nam, Je-Yoel Cho","doi":"10.1038/s41416-026-03517-8","DOIUrl":"10.1038/s41416-026-03517-8","url":null,"abstract":"Characterising somatic mutation profiles in human breast cancer (HBC) is essential for understanding tumour progression and guiding therapeutic strategies. We performed genomic and transcriptomic analyses to profile the mutational landscape of HBC. In addition to our primary analysis of HBC, we conducted comparative genomic analyses to evaluate the extent to which these mutational processes are recapitulated in canine mammary tumour (CMT), a widely proposed translational model. APOBEC3 (A3)-associated mutations were extensive in HBC but largely absent in CMT, likely due to structural differences in A3 proteins and lower basal expression. Transcriptomic stratification of HBC by A3 activity uncovered that tumours with A3 activity showed a strong association with the PAM50-HER2-Enriched (HER2E) subtype, and FGFR4 was significantly correlated with the expression and enzymatic function of APOBEC3A/B. These findings demonstrate that CMT is an unsuitable model for A3-mediated mutagenesis, emphasising the need to consider the limitations of cross-species mutational modelling in comparative oncology. Moreover, this study identifies a potential regulatory association between FGFR4 and A3, offering insights into the underlying mechanisms of A3-driven mutagenesis and suggesting that the FGFR4-A3 activity could be considered alongside other molecular biomarkers for the classification of the HER2E subtype.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1483-1498"},"PeriodicalIF":7.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03517-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDAC6 is a biomarker of leukaemic dissemination and relapse in B-ALL","authors":"Karina E. Jiménez-Camacho, Hilda Vargas-Robles, Joseph Adomako, Ana Beatriz Sánchez-Argáez, M. Victor M. Correa-Lara, Antonio Sandoval-Cabrera, Elisa Dorantes-Acosta, Juan Manuel Mejía-Aranguré, Sara Castañeda-Contreras, Juan Carlos Núñez-Enríquez, Minerva Mata-Rocha, Rosana Pelayo, Michael Schnoor","doi":"10.1038/s41416-026-03539-2","DOIUrl":"10.1038/s41416-026-03539-2","url":null,"abstract":"Relapse remains the leading cause of treatment failure in B-cell acute lymphoblastic leukaemia (B-ALL), highlighting the need for biomarkers and therapeutic targets that limit leukaemic dissemination. We investigated whether histone deacetylase 6 (HDAC6), a regulator of cortactin-dependent actin remodelling, contributes to B-ALL progression and relapse. HDAC6 expression was analysed in cohorts of 72 paediatric and 54 adult patients with B-ALL and validated in B-ALL cell lines. The functional role of HDAC6 was assessed using pharmacological inhibition and shRNA-mediated knockdown in assays of CXCL12-induced actin remodelling, transendothelial migration, bone marrow colonisation and leukaemic dissemination in vivo. Cortactin-depleted cells were used to determine pathway dependence. HDAC6 expression was elevated in B-ALL cell lines and patient samples and was significantly associated with relapse in both patient cohorts. Pharmacological inhibition or genetic depletion of HDAC6 impaired CXCL12-induced actin remodelling, transendothelial migration, bone marrow colonisation and leukaemic dissemination. HDAC6 inhibition failed to further reduce migration in cortactin-deficient cells, indicating that HDAC6 promotes leukaemic motility through cortactin. HDAC6 is a clinically relevant biomarker associated with B-ALL relapse and a critical regulator of cortactin-dependent leukaemic dissemination. Targeting HDAC6 represents a promising therapeutic strategy to limit tissue invasion and reduce relapse.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1470-1482"},"PeriodicalIF":7.8,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03539-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Romiplostim for chemotherapy induced thrombocytopenia in pediatric cancers","authors":"Shivam Bansal, Aditya Kumar Gupta, Jagdish Prasad Meena, Tushar Sehgal, Rachna Seth","doi":"10.1038/s41416-026-03561-4","DOIUrl":"10.1038/s41416-026-03561-4","url":null,"abstract":"Chemotherapy-induced-thrombocytopenia (CIT) compromises cancer care, but data on its management in children is scarce. Romiplostim, a thrombopoietin-receptor-agonist, has shown efficacy in adults with CIT, though its role in paediatric patients remains undefined. We conducted an investigator-initiated, open-label, randomized-controlled-trial at a tertiary center in India to evaluate prophylactic romiplostim for prevention of CIT in children aged 1-14 years with acute myeloid leukemia (AML), non-Hodgkin’s lymphoma (NHL), and solid-tumors receiving myelosuppressive chemotherapy. Patients were randomly assigned (1:1) to receive romiplostim (3 μg/kg-subcutaneously) or standard-care. The primary outcome was platelet recovery (≥100 × 10⁹/L and transfusion-free for 72 hours) within 3-weeks. Secondary outcomes included bleeding, transfusion requirements, chemotherapy delays, and immature platelet fraction percentagecIPF%) trends. From March 2023 to October 2024, 93 patients (median age, 3 years; interquartile range [IQR], 2–5) were randomized (47 intervention, 46 control). Platelet recovery occurred in 91.3% and 88.1%, respectively (risk difference, 3.2 percentage points; 95% confidence interval [CI], –9.5 to 15.9; P = 0.73). Clinically significant bleeding (≥WHO grade 2) occurred in none of 46 patients in romiplostim group and 6 of 43 (14%) in control group (absolute risk difference,–14 percentage points; 95% CI, –27 to –2; P = 0.01). Median platelet transfusion volume was lower with romiplostim (19.3 vs. 29.6 mL/kg; median difference, –10.3 mL/kg; 95% CI, –21.5 to 0.9; P = 0.06, rank-biserial correlation= 0.35). Romiplostim significantly increased IPF% on day-16 from baseline (258% vs. 47.7%, p = 0.016, Cohen’s h = 2.41). No thrombotic events occurred. Prophylactic romiplostim didn’t hasten platelet recovery in pediatric patients receiving myelosuppressive chemotherapy but was associated with reduced bleeding and had lower transfusion requirements. There was a significant relative immature platelet fraction percentage (IPF)% increment on day 16 in the romiplostim arm in comparison to the control arm, reinforcing the biological plausibility of romiplostim’s effect on megakaryocyte stimulation. Clinical Trials Registry of India: CTRI/2023/02/049906.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1417-1423"},"PeriodicalIF":7.8,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid metabolic reprogramming of macrophage by host APOBEC3 deficiency enhances anti-tumor immunity","authors":"Yuqi Yang, Fanglin Li, Mozi Lei, Yi Liu, Jiangling Lu, Chen Chen, Danyang Cui, Yiru Long, Xiaolu Yu, Jianhua Sun, Jing Chen, Nan Liu, Bingshun Wang, Likun Gong","doi":"10.1038/s41416-026-03550-7","DOIUrl":"10.1038/s41416-026-03550-7","url":null,"abstract":"Tumour-associated macrophages are an indispensable part of the tumour immune microenvironment, exhibiting phenotypic and functional plasticity that enables them to play an important role in modulating the immune response. A large number of RNA editing events have been identified during macrophage functional remodelling. APOBEC3 is a well-known family of base-editing enzymes, but whether and how it regulates macrophage function is unclear. In this study, we mainly used genetically engineered mice to demonstrate how host APOBEC3 deficiency affects tumour progression. We found that the polarisation state of macrophages in the tumour microenvironment was altered by host APOBEC3 deficiency and that knockout of host APOBEC3 significantly inhibited tumour growth and metastasis in a macrophage-dependent manner. Moreover, APOBEC3 deficiency remodelled macrophage function, improved their polarisation state, and enhanced their phagocytic capacity. Mechanistically, APOBEC3 knockout attenuated lipid uptake by macrophages in a PPARγ pathway-dependent way, leading to an increase of M1/M2 ratio in macrophages. These findings reveal that APOBEC3 deficiency drives lipid metabolism reprogramming in macrophages and remodels their functions, thereby inducing a strong anti-tumour immune response, providing a proof-of-concept and new insights for the development of the APOBEC3 family for novel tumour therapies.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 8","pages":"1220-1231"},"PeriodicalIF":7.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese expert consensus on precision testing and molecular diagnosis of pancreatic cancer (2025)","authors":"Dan Cao, Jianhui Wu, Jiujie Cui, Chen Xun, Jun Zhou, Wei Li, Jinghua Sun, Liu Yang, Ke Cheng, Huanji Xu, Guanghai Dai, Kuirong Jiang, Qi Li, Guang Tan, Hongmei Zhang, Tao Zhang, Zhihong Zhang, Chunyi Hao, Liwei Wang, Shukui Qin","doi":"10.1038/s41416-026-03522-x","DOIUrl":"10.1038/s41416-026-03522-x","url":null,"abstract":"This consensus by the CSCO Pancreatic Cancer Expert Committee establishes evidence-based guidelines for molecular testing in pancreatic ductal adenocarcinoma. It details recommendations for biomarkers (e.g., KRAS, BRCA, MSI), liquid biopsy, and precision imaging to direct targeted therapies and immunotherapy, aiming to standardize diagnosis and optimize individualized patient care. Pancreatic ductal adenocarcinoma (PDAC) is the most common pathological type of primary pancreatic malignancy, accounting for ~95% of cases and generally referred to as pancreatic cancer [1]. Its prognosis is extremely poor and its incidence continues to rise [2]. According to the most recent global cancer statistics, the incidence of pancreatic cancer ranks 12th among all cancers, and its mortality ranks 6th, making it one of the deadliest malignancies worldwide [3]. Approximately 57% of patients have metastatic disease at diagnosis and require systemic therapy, for which chemotherapy remains the standard first-line option [1]. However, the overall response rate to currently available systemic regimens is low, and the 5-year survival rate for patients with metastatic disease remains below 5% [3]. Although most pancreatic cancers harbor canonical driver mutations, they exhibit marked heterogeneity at the molecular level. Whole-genome sequencing (WGS) and integrative genomic analyses have identified molecular subtypes of PDAC with potential clinical relevance [4–9]. With the increasing implementation of precision oncology, the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Pancreatic Cancer give a level 1 recommendation to perform genetic and other molecular testing on tissue or cytologic specimens as part of the pathological diagnostic work-up, in order to guide individualized treatment, including targeted therapy and immunotherapy [10]. To further promote the use of genetic and molecular testing in the precision treatment of pancreatic cancer, the CSCO Pancreatic Cancer Expert Committee convened a multidisciplinary panel to develop the present Chinese Expert Consensus on Precision Testing and Molecular Diagnosis of Pancreatic Cancer (2025), aiming to provide clinicians with an authoritative reference for precision diagnostics and treatment decision-making.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 6","pages":"845-855"},"PeriodicalIF":7.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose triglyceride lipase driven lipolysis as a targetable metabolic vulnerability in prostate cancer with intrinsic metabolic inflexibility","authors":"Andreas Tiefenbacher, Madeleine Gudenus, Daniel Valcanover, Barbara Neudert, Raheleh Sheibani-Tezerji, Theresa Mendrina, Jessica Kalla, Laura Pajed, Kristina Draganić, Andrea Haitel, Astrid Haase, Markus Hartenbach, Sazan Rasul, Walter Berger, Rolf Breinbauer, Gernot Grabner, Martina Schweiger, Eva Compérat, Gerda Egger","doi":"10.1038/s41416-026-03545-4","DOIUrl":"10.1038/s41416-026-03545-4","url":null,"abstract":"Despite the widespread clinical use of prostate-specific membrane antigen (PSMA)-targeted imaging and therapy in prostate cancer, the biological functions underlying PSMA-associated tumour aggressiveness remain incompletely understood. PSMA-PET-guided sampling of paired PSMA-high and PSMA-low tumour regions was used for integrated proteomic and epigenomic analyses. PSMA-ATGL correlation was validated by immunohistochemistry in 90 treatment-naïve patients. Metabolic profiling was performed using Seahorse Mito Fuel Flex Test assays under unperturbed conditions and pharmacological or genetic perturbation of ATGL and PSMA. Therapeutic vulnerability was assessed using NG-497 and siRNA-mediated knockdown. PSMA-high tumours exhibited lipolytic reprogramming characterised by ATGL upregulation, confirmed by a robust PSMA-ATGL correlation in the validation cohort (P < 0.0001). Despite shared fatty acid dependency, LNCaP cells exhibited intrinsic metabolic inflexibility while 22RV1 cells displayed high adaptability. Both pharmacological and genetic ATGL inhibition most potently impaired LNCaP proliferation. Enzalutamide upregulated ATGL in both cell lines, revealing reciprocal regulation between AR signaling and the PSMA/ATGL axis. ATGL-mediated lipolysis represents a promising therapeutic target in prostate cancer, with heightened sensitivity in tumours lacking metabolic flexibility to utilize alternative pathways.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 8","pages":"1342-1355"},"PeriodicalIF":7.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03545-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}