Functional CRISPR screen towards identifying novel epigenetic co-factors of oncogenic AR-activity

摘要: Prostate cancer (PCa) is the second leading cause of cancer-related mortality in North American men. In recent years, there has been mounting evidence establishing the centrality of epigenetic mechanisms in PCa initiation and progression. Accordingly, various epigenetic genes have been described to collaborate with the androgen receptor (AR) in enabling its oncogenic transcriptional program and aberrantly restoring its activity in metastatic castration resistant PCa. Concordantly, our laboratory has recently described two epigenetic genes, BRD4 and MLL2, as key co-activators of AR-signaling. Furthermore, we have demonstrated that inhibition of these genes synergistically work with AR antagonists to attenuate PCa progression in preclinical models. Thus, in a setting where all metastatic patients eventually progress to evolve resistance to anti-AR therapies, there exists a dire clinical need to identify novel …