Methylation profile of neuroendocrine prostate cancer models
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA449098 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6956234.fastq.gz | Fastqsanger.gz | |||
| SRR6956235.fastq.gz | Fastqsanger.gz | |||
| SRR6956236.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
Similar Datasets
Project description:Neuroendocrine prostate cancer models
| PRJNA449097 | ENA
Project description:Our study represents a detailed molecular analysis of neuroenedocrine prostate cancer models
2018-06-22 | GSE112829 | 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:EZH2 has differential activity in prostate adenocarcinoma and neuroendocrine prostate cancer.
2024-07-16 | GSE256219 | GEO
Project description:Aberrant DNA methylation has been implicated as a key driver of prostate cancer lineage plasticity and histologic transformation to neuroendocrine prostate cancer (NEPC). DNA methyltransferases (DNMT) are highly expressed, and global DNA methylation levels are elevated in NEPC. We identified that deletion of DNMT genes decreases expression of neuroendocrine lineage markers and markedly reduced NEPC tumor development and metastasis in vivo. Decitabine, a global DNMT inhibitor, significantly attenuated tumor growth in NEPC patient-derived xenograft (PDX) models, as well as RB1-deficient castration-resistant prostate adenocarcinoma (CRPC) models compared with RB1-proficient CRPC. We further discovered that DNMT inhibition increased expression of B7-H3, an emerging druggable target, via demethylation of B7-H3 CpG islands. We tested DS-7300a, a novel antibody-drug conjugate (ADC) targeting B7-H3, alone and in combination with decitabine. There was potent single agent antitumor activity of DS-7300a in both CRPC and NEPC models bearing high expression of B7-H3. In B7-H3 low models, combination therapy of decitabine plus DS-7300a resulted in a synergistic response. Overall, we report that DNMT inhibition is a novel therapeutic target for NEPC and RB1-deficient CRPC and may sensitize B7-H3-low prostate cancer to the ADC DS-7300a through increasing target expression. NEPC and RB1-deficient CRPC represent prostate cancer subgroups with poor prognosis. The development of novel biomarker-driven therapeutic strategies for this population may ultimately help improve patient outcomes.
2024-03-27 | GSE216050 | GEO
Project description:Aberrant DNA methylation has been implicated as a key driver of prostate cancer lineage plasticity and histologic transformation to neuroendocrine prostate cancer (NEPC). DNA methyltransferases (DNMT) are highly expressed, and global DNA methylation levels are elevated in NEPC. We identified that deletion of DNMT genes decreases expression of neuroendocrine lineage markers and markedly reduced NEPC tumor development and metastasis in vivo. Decitabine, a global DNMT inhibitor, significantly attenuated tumor growth in NEPC patient-derived xenograft (PDX) models, as well as RB1-deficient castration-resistant prostate adenocarcinoma (CRPC) models compared with RB1-proficient CRPC. We further discovered that DNMT inhibition increased expression of B7-H3, an emerging druggable target, via demethylation of B7-H3 CpG islands. We tested DS-7300a, a novel antibody-drug conjugate (ADC) targeting B7-H3, alone and in combination with decitabine. There was potent single agent antitumor activity of DS-7300a in both CRPC and NEPC models bearing high expression of B7-H3. In B7-H3 low models, combination therapy of decitabine plus DS-7300a resulted in a synergistic response. Overall, we report that DNMT inhibition is a novel therapeutic target for NEPC and RB1-deficient CRPC and may sensitize B7-H3-low prostate cancer to the ADC DS-7300a through increasing target expression. NEPC and RB1-deficient CRPC represent prostate cancer subgroups with poor prognosis. The development of novel biomarker-driven therapeutic strategies for this population may ultimately help improve patient outcomes.
2024-03-27 | GSE216712 | GEO
Project description:Aberrant DNA methylation has been implicated as a key driver of prostate cancer lineage plasticity and histologic transformation to neuroendocrine prostate cancer (NEPC). DNA methyltransferases (DNMT) are highly expressed, and global DNA methylation levels are elevated in NEPC. We identified that deletion of DNMT genes decreases expression of neuroendocrine lineage markers and markedly reduced NEPC tumor development and metastasis in vivo. Decitabine, a global DNMT inhibitor, significantly attenuated tumor growth in NEPC patient-derived xenograft (PDX) models, as well as RB1-deficient castration-resistant prostate adenocarcinoma (CRPC) models compared with RB1-proficient CRPC. We further discovered that DNMT inhibition increased expression of B7-H3, an emerging druggable target, via demethylation of B7-H3 CpG islands. We tested DS-7300a, a novel antibody-drug conjugate (ADC) targeting B7-H3, alone and in combination with decitabine. There was potent single agent antitumor activity of DS-7300a in both CRPC and NEPC models bearing high expression of B7-H3. In B7-H3 low models, combination therapy of decitabine plus DS-7300a resulted in a synergistic response. Overall, we report that DNMT inhibition is a novel therapeutic target for NEPC and RB1-deficient CRPC and may sensitize B7-H3-low prostate cancer to the ADC DS-7300a through increasing target expression. NEPC and RB1-deficient CRPC represent prostate cancer subgroups with poor prognosis. The development of novel biomarker-driven therapeutic strategies for this population may ultimately help improve patient outcomes.
2024-03-27 | GSE216713 | 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: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