{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jimenez-Vacas JM"],"funding":["Royal Society of Medicine","Prostate Cancer Foundation (PCF)","Royal Society of Medicine (RSM)","NCI NIH HHS","Prostate Cancer Foundation","Wellcome Trust"],"pagination":["8806"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12508096"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease requiring additional therapeutic strategies. MCL1, an anti-apoptotic BCL2 family member, promotes cancer-cell survival, but its role in mCRPC remains poorly understood. Here, we characterise MCL1 in multiple mCRPC biopsy cohorts and patient-derived models, assessing responses to MCL1 inhibition. MCL1 copy number gain (14%-34%) correlates with increased MCL1 expression and worse outcomes. MCL1 inhibition exhibits anti-tumour effects in MCL1-gained mCRPC models. Co-inhibition of MCL1 and AKT induces cancer-specific cell death in PTEN-loss/PI3K-activated models in vitro and in vivo, modulating BAD-BCLXL and BIM-MCL1 interactions, with durable anti-tumour activity in models with AKT inhibitor acquired resistance. Final"],"journal":["Nature communications"],"pubmed_title":["Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer."],"pmcid":["PMC12508096"],"funding_grant_id":["R50 CA274336","Clinical Research Career Development Fellowship","P01 CA163227","R21 CA277368","IES\\R3\\213131","Challenge Award"],"pubmed_authors":["Galipeau P","Lambros M","Buroni L","Bertan C","Riisnaes R","Taylor J","Rekowski J","Seed G","Balk SP","Yuan W","Welti J","Ha G","Jimenez-Vacas JM","Chau CH","Hobern E","Coleman I","Zeng W","Karzai F","Thomas CJ","Neeb AJ","Wilkinson S","Bezzi M","Crespo M","Gabel F","Valenti M","Sharp A","Padilha A","Das S","de Bono JS","Bogdan D","Carreira S","Waldron N","Westaby D","De Haven Brandon A","Beatson EL","Liodaki K","Varkaris A","Trostel SY","Gurel B","Persse T","Nelson PS","Swain A","Paravati R","Raynaud F","Figueiredo I","Klumpp-Thomas C","Pandell N","Ferreira A","Luque RM","Miranda S","Ning J","Montero-Hidalgo AJ","Figg WD","Sowalsky AG","Bernett I","Lack NA","Zhang X","Yu IPL"],"additional_accession":[]},"is_claimable":false,"name":"Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer.","description":"Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease requiring additional therapeutic strategies. MCL1, an anti-apoptotic BCL2 family member, promotes cancer-cell survival, but its role in mCRPC remains poorly understood. Here, we characterise MCL1 in multiple mCRPC biopsy cohorts and patient-derived models, assessing responses to MCL1 inhibition. MCL1 copy number gain (14%-34%) correlates with increased MCL1 expression and worse outcomes. MCL1 inhibition exhibits anti-tumour effects in MCL1-gained mCRPC models. Co-inhibition of MCL1 and AKT induces cancer-specific cell death in PTEN-loss/PI3K-activated models in vitro and in vivo, modulating BAD-BCLXL and BIM-MCL1 interactions, with durable anti-tumour activity in models with AKT inhibitor acquired resistance. Final","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-04T09:25:49.395Z","creation":"2026-05-07T03:12:33.052Z"},"accession":"S-EPMC12508096","cross_references":{"pubmed":["41062500"],"doi":["10.1038/s41467-025-64042-5"]}}