{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Thienger P"],"funding":["NCI NIH HHS"],"pubmed_abstract":["Proteolysis targeting chimera (PROTAC) therapies degrading SWI/SNF ATPases offer a novel approach to interfere with androgen receptor (AR) signaling in AR-dependent castration-resistant prostate cancer (CRPC-AR). To explore the utility of SWI/SNF therapy beyond AR-sensitive CRPC, we investigated SWI/SNF-targeting agents in AR-negative CRPC. SWI/SNF targeting PROTAC treatment of cell lines and organoid models reduced the viability of not only CRPC-AR but also WNT-signaling dependent AR-negative CRPC (CRPC-WNT). The CRPC-WNT subgroup represents 11% of around 400,000 cases of CRPC worldwide who die yearly of CRPC. We discovered that SWI/SNF ATPase SMARCA4 depletion interfered with the master transcriptional regulator TCF7L2 (TCF4) in CRPC-WNT. Functionally, TCF7L2 maintains proliferation via "],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.03.24.586276"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12424701"],"repository":["biostudies-literature"],"pubmed_title":["A double-negative prostate cancer subtype is vulnerable to SWI/SNF-targeting degrader molecules."],"pmcid":["PMC12424701"],"funding_grant_id":["P50 CA275741"],"pubmed_authors":["Shah SR","Triscott J","Lillis N","Shi M","Quigley DA","Yu H","Paassen I","Cassanmagnago GA","Daniel B","Chen Y","Lehner M","Rubin PD","Bolis M","Thienger P","Leung AK","Yauch RL","Piscuoglio S","Yao X","Naveed A","Benjak A","de Brot S","Tremblay J","Beltran H","Rubin MA","Mela L","Ng CKY"],"additional_accession":[]},"is_claimable":false,"name":"A double-negative prostate cancer subtype is vulnerable to SWI/SNF-targeting degrader molecules.","description":"Proteolysis targeting chimera (PROTAC) therapies degrading SWI/SNF ATPases offer a novel approach to interfere with androgen receptor (AR) signaling in AR-dependent castration-resistant prostate cancer (CRPC-AR). To explore the utility of SWI/SNF therapy beyond AR-sensitive CRPC, we investigated SWI/SNF-targeting agents in AR-negative CRPC. SWI/SNF targeting PROTAC treatment of cell lines and organoid models reduced the viability of not only CRPC-AR but also WNT-signaling dependent AR-negative CRPC (CRPC-WNT). The CRPC-WNT subgroup represents 11% of around 400,000 cases of CRPC worldwide who die yearly of CRPC. We discovered that SWI/SNF ATPase SMARCA4 depletion interfered with the master transcriptional regulator TCF7L2 (TCF4) in CRPC-WNT. Functionally, TCF7L2 maintains proliferation via ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-04-16T03:21:44.45Z","creation":"2026-04-16T03:12:45.909Z"},"accession":"S-EPMC12424701","cross_references":{"pubmed":["40949972"],"doi":["10.1101/2024.03.24.586276"]}}