Identifying Androgen Receptor-Independent Mechanisms of Prostate Cancer Resistance to Second-Generation Antiandrogen Therapy
Technical Report,01 Aug 2015,31 Jul 2016
Sloan Kettering Institute for Cancer Research New York United States
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We hypothesize that GR mediates resistance to enzalutamide in advanced prostate cancer through transactivation of SGK1. In this proposal, we aim to further explore the relationship between GR, SGK1, and enzalutamide resistance through experimental manipulation of GR and SGK1 in our previously reported laboratory models of enzalutamide resistance. In this research period we have further expanded upon the relationship between GR and SGK1 in the context of enzalutamide-driven prostate cancer. We have generated CRISPRCas9 cell lines to test the importance of SGK1. Finally, we have used the recently published metastatic prostate cancer genomics dataset to identify a novel mechanism of enzalutamide resistance that correlates with the effects of SGK1 in our xenograft models. This project has the potential to identify a critical and druggable component of the GR program to enable a safer and more effective strategy for treating AR-independent enzalutamide-resistant prostate cancers.
- Medicine and Medical Research
- Anatomy and Physiology