Cotargeting of Androgen Synthesis and Androgen Receptor Expression as a Novel Treatment for Castration-Resistant Prostate Cancer
Abstract
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 targeting PRMT5 with BLL3.3 in combination with abiraterone or enzalutamide is more effective in killing CRPC cells. In addition, we also found that PRMT5 expression correlates with AR expression at mRNA levels and knockdown of PRMT5 suppresses 22Rv1 xenograft tumor growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2018
- Accession Number
- AD1059215
Entities
People
- Chang-deng Hu
- Elena Beketova
- Jake L Owens
- Jonathan Malola
- Xuehong Deng
Organizations
- Purdue University