Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen/AR-targeted therapy.

ABSTRACT: Despite recent advances, the efficacy of androgen/androgen receptor (AR)-targeted therapy remains  limited for many patients with metastatic prostate cancer. This is in part because prostate cancers adaptively switch to the androgen/AR-independent pathway for survival and growth, thereby conferring therapy resistance. Tumor hypoxia is considered as a major cause of treatment resistance. However, the exact mechanism is largely unclear. Here we report that chronic-androgen deprivation therapy (ADT) in the condition of hypoxia induces adaptive androgen/AR-independence, and therefore confers resistance to androgen/AR-targeted therapy, e.g., enzalutamide. Mechanistically, this is mediated by glucose-6-phosphate isomerase (GPI), which is transcriptionally repressed by AR in hypoxia, but restored

SUBMITTER: Geng H 

PROVIDER: S-EPMC6255907 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature