Cotargeting of Androgen Synthesis and Androgen Receptor Expression as a Novel Treatment for Castration-Resistant Prostate Cancer
Abstract
Prostate cancer is the second leading cause of cancer death among American men in 2019. 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 further validated pIC1n as a cofactor of PRMT5 to regulate AR expression. We have also characterized a novel PRMT5 inhibitor from Johnson and Johnson as a potential pharmacological tool to evaluate the role of PRMT5 in prostate cancer. We will extend current findings and complete all planned experiments.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1109482
Entities
People
- Chang-deng Hu
- Elena Beketova
- Jake L Owens
- Jogendra Singh Pawar
- Xuehong Deng
Organizations
- Purdue University