What question did this study set out to answer?

To identify the genetic drivers and molecular mechanisms that govern lineage plasticity, metastasis, and antiandrogen therapy resistance in prostate cancer.

January 5, 2017Science

Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance

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Authors

SKSheng‐Yu KuBroad Institute SRSpencer R. RosarioRoswell Park Comprehensive Cancer Center YWYanqing WangOcean University of China

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Implication

Preclinical study reveals that Rb1 and Trp53 loss drives prostate cancer lineage plasticity and drug resistance, indicating that Ezh2 inhibition can restore antiandrogen sensitivity.

Key Points

To identify the genetic drivers and molecular mechanisms that govern lineage plasticity, metastasis, and antiandrogen therapy resistance in prostate cancer.
Generated genetically engineered mouse models harboring conditional deletions of Pten, Rb1, and Trp53 to examine tumor evolution and metastatic capability.
Performed gene expression profiling comparing mouse tumors with human neuroendocrine prostate cancer variants and evaluated pharmacological Ezh2 inhibitors.
Loss of Rb1 promoted lineage plasticity and metastasis in Pten-deficient prostate adenocarcinoma, whereas the simultaneous deletion of Trp53 conferred resistance to antiandrogen therapy.
Mouse and human resistant tumors exhibited shared neuroendocrine gene signatures characterized by elevated expression of epigenetic reprogramming factors, including Ezh2 and Sox2.
Treatment with clinically relevant Ezh2 inhibitors reestablished androgen receptor expression and resensitized tumors to antiandrogen treatment.

Cite This Study

Ku et al. (2017) studied this question.

synapsesocial.com/papers/69dbdfd59e6f14d6f1684958 https://doi.org/10.1126/science.aah4199

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Implication

Preclinical study reveals that Rb1 and Trp53 loss drives prostate cancer lineage plasticity and drug resistance, indicating that Ezh2 inhibition can restore antiandrogen sensitivity.

Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance

Discussion

Member takes

Implication

Key Points

Cite This Study

Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance

Discussion

Member takes

Implication

Key Points

Cite This Study

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