GEO series
Castrate Resistant Prostate Cancer Response to Taxane is Determined by an HNF1-dependent Apoptosis Resistance Circuit (ChIP-Seq)
GSE252203
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing
16 samples
2024/04/01
GPL24676
Summary
Metastatic castrate-resistant prostate cancer (mCRPC) is a genetically and phenotypically heterogeneous cancer where advancements are needed in biomarker discovery and targeted therapy. A critical and often effective component of treatment includes taxanes. We performed one of the first high throughput screens across a cohort of 30 diverse patient-derived CRPC organoids to a library of 78 drugs. Combining quantitative response measures with transcriptomic analyses demonstrated that HNF1 Homeobox A (HNF1A) drives a transcriptional program of taxane resistance, dependent upon cellular inhibitor of apoptosis protein 2 (cIAP2). Monotherapy with cIAP2 inhibitor LCL161 was sufficient to treat HNF1A+ models of mCRPC previously resistant to docetaxel.
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Paper (PMID 39657662) ↗
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