An androgen receptor switch underlies lineage infidelity to drive neuroendocrine prostate cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA575909 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10233355_1.fastq.gz | Fastqsanger.gz | |||
| SRR10233355_2.fastq.gz | Fastqsanger.gz | |||
| SRR10233356_1.fastq.gz | Fastqsanger.gz | |||
| SRR10233356_2.fastq.gz | Fastqsanger.gz | |||
| SRR10233357_1.fastq.gz | Fastqsanger.gz |
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Project description:Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC tumors may also express neuroendocrine markers, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests kinase signaling may be an important driver of NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing AR-negative to AR-positive prostate cancer cell lines and identified multiple altered signaling pathways, including enrichment of RET kinase activity in the AR-negative cell lines. Clinical NEPC and NEPC patient derived xenografts displayed upregulated RET transcript and RET pathway activity. Pharmacologically inhibiting RET kinase in NEPC models dramatically reduced tumor growth and cell viability in mouse and human NEPC models. Our results suggest that targeting RET in NEPC tumors with high RET expression may be a novel treatment option.
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