A Drug Repurposing Screen Identifies Fludarabine Phosphate as a Potential Therapeutic Agent for N-MYC Overexpressing Neuroendocrine Prostate Cancers.

ABSTRACT: Neuroendocrine prostate cancer (NEPC) represents a highly aggressive form of prostate tumors. NEPC results from trans-differentiated castration-resistant prostate cancer (CRPC) with increasing evidence indicating that the incidence of NEPC often results from the adaptive response to androgen deprivation therapy. Recent studies have shown that a subset of NEPC exhibits overexpression of the MYCN oncogene along with the loss of tumor suppressing TP53 and RB1 activities. N-MYC is structurally disordered with no binding pockets available on its surface and so far, no clinically approved drug is available. We adopted a drug-repurposing strategy, screened ~1800 drug molecules, and identified fludarabine phosphate to preferentially inhibit the proliferation of N-MYC overexpressing NEPC cel

SUBMITTER: Elhasasna H 

PROVIDER: S-EPMC9317991 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature