Accession Number : AD1042920


Title :   P52 Activation and Enzalutamide Therapy in Prostate Cancer


Descriptive Note : Technical Report,30 Sep 2016,29 Sep 2017


Corporate Author : University of California, Davis Sacramento United States


Personal Author(s) : Gao, Allen C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1042920.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 7


Abstract : There has been a major focus on the androgen receptor (AR) pathway as the principal therapeutic target for CRPC including recently approved therapies such as next-generation antiandrogen enzalutamide and abiraterone. Despite these advances that provide temporary respite, almost all patients will go on to die from progressive and resistant prostate cancer. Therefore, there is an urgent need to identify resistant pathways that perpetuate disease progression. We provided preliminary data demonstrating that p52 increases AR variant V7 (AR-V7) expression and enhances prostate cancer cell resistance to next generation antiandrogen enzalutamide treatment. We hypothesize that overexpression of p52 signaling activates resistance pathways to enzalutamide and co-targeting p52 will overcome treatment resistance. In this project, we will examine the potential mechanisms underlying p52-mediated treatment resistance (Aim 1). Aim 2 will validate the efficacy of co-targetingp52 to overcome treatment resistance to enzalutamide. We hope to identify the mechanisms of adaptive/resistant pathways that are responsible for enzalutamide resistance, and provide a rationale for therapeutic co-targeting to overcome enzalutamide resistance


Descriptors :   prostate cancer , neoplasms , proteins , therapeutics , resistance , disease attributes , transcription factors , cell physiological processes , Androgens


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE