Molecular Basis of Neuroendocrine Prostate Cancer
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ABSTRACT:
PROVIDER: PRJNA282856 | ENA |
REPOSITORIES: ENA
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Project description:Neuroendocrine prostate cancer models
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Project description:Neuroendocrine prostate cancer (NEPC) is a subset of castration-resistant prostate cancer (CRPC) and is thought to derive from prostate adenocarcinoma. However, the cellular basis responsible for Neuroendocrine differentiation (NED) is still under debate. Here, we characterized the tumor cell diversity of 6 CRPC patients using single cell RNA sequencing (scRNA-seq) and detected NED in four patients.
2020-09-01 | GSE137829 | GEO
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.
2020-05-29 | PXD012971 | Pride
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.
2020-05-29 | PXD012970 | Pride
Project description:Neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (CRPC). The molecular mechanisms underlying the progression of CRPC toward NEPC remain incompletely understood and effective treatments remain to be discovered. Herein, we report that loss of the nuclear receptor ERRγ promotes neuroendocrine differentiation in a Pten-deficient mouse model of prostate adenocarcinoma. These findings were recapitulated in advanced cellular and xenograft models of human prostate cancer (PCa). Critically, we show that ERRγ gain-of-function can reverse instilled NEPC features accompanied by suppression of growth and oncogenic metabolic reprogramming. Activation of a neuroendocrine transcriptional program enabled by ERRγ deficiency unveiled a targetable vulnerability exploited by combined pharmacological inhibition of EZH2 and RET kinase that effectively inhibited the growth of ERRγ-deficient tumor organoids and cells. Collectively, our findings demonstrate that ERRγ downregulation facilitates PCa adeno-to-neuroendocrine transformation and offer potential therapeutic strategies to prevent/treat the development of poor outcome NEPC.
2025-10-29 | GSE248844 | GEO
Project description:Neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (CRPC). The molecular mechanisms underlying the progression of CRPC toward NEPC remain incompletely understood and effective treatments remain to be discovered. Herein, we report that loss of the nuclear receptor ERRγ promotes neuroendocrine differentiation in a Pten-deficient mouse model of prostate adenocarcinoma. These findings were recapitulated in advanced cellular and xenograft models of human prostate cancer (PCa). Critically, we show that ERRγ gain-of-function can reverse instilled NEPC features accompanied by suppression of growth and oncogenic metabolic reprogramming. Activation of a neuroendocrine transcriptional program enabled by ERRγ deficiency unveiled a targetable vulnerability exploited by combined pharmacological inhibition of EZH2 and RET kinase that effectively inhibited the growth of ERRγ-deficient tumor organoids and cells. Collectively, our findings demonstrate that ERRγ downregulation facilitates PCa adeno-to-neuroendocrine transformation and offer potential therapeutic strategies to prevent/treat the development of poor outcome NEPC.
2025-10-29 | GSE291072 | GEO
Project description:ERRγ impedes neuroendocrine prostate cancer development
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Project description:We report the generation and characterization of tumor organoids and PDOX derived from needle biopsies of metastatic lesions from neuroendocrine prostate cancer patients.
2018-06-22 | GSE112786 | GEO
Project description:We profiled the epigenomes of neuroendocrine prostate cancer and prostate adenocarcinoma patient-derived xenografts using ChIP-seq for transcription factors and histone modifications.
2020-11-22 | GSE161948 | GEO
Project description:Molecular characterization of neuroendocrine prostate cancer organoids and PDOX by RNA-seq
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