Cotargeting of Androgen Synthesis and Androgen Receptor Expression as a Novel Treatment for Castration-Resistant Prostate Cancer
Technical Report,01 Aug 2016,31 Jul 2017
Purdue University West Lafayette United States
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Prostate cancer is the third leading cause of cancer death among American men in 2017. The majority of the death is due to the development of castration resistant prostate cancer CRPC after androgen deprivation therapy ADT. Despite the development and use of next generation anti-AR signaling inhibitors ASI such as abiraterone and enzalutamide, resistance to ASI remains the major clinical challenge. The proposed research is based on the finding that protein arginine methyltransferase 5 PRMT5 is a novel epigenetic activator of AR transcription. If PRMT5 targeting can inhibit or eliminate AR transcription, combining PRMT5 targeting with androgen synthesis inhibition should exhibit a better treatment effect for CRPC. During the past grant period, we have successfully demonstrated that PRMT5 also epigenetically regulates the expression of both AR and AR-V7 in CRPC cells, and that knockdown or inhibition of PRMT5 suppresses growth of CRPC cells. These results support our hypothesis, and we will continue to test our hypothesis during next grant period.