Blocking PI3K p110β Attenuates Development of PTEN-Deficient Castration-Resistant Prostate Cancer.

ABSTRACT: A common outcome of androgen deprivation in prostate cancer therapy is disease relapse and progression to castration-resistant prostate cancer (CRPC) via multiple mechanisms. To gain insight into the recent clinical findings that highlighted genomic alterations leading to hyperactivation of PI3K, we examined the roles of the commonly expressed p110 catalytic isoforms of PI3K in a murine model of Pten-null invasive CRPC. While blocking p110α had negligible effects in the development of Pten-null invasive CRPC, either genetic or pharmacologic perturbation of p110β dramatically slowed CRPC initiation and progression. Once fully established, CRPC tumors became partially resistant to p110β inhibition, indicating the acquisition of new dependencies. Driven by our genomic analyses highlighting po

SUBMITTER: Gao X 

PROVIDER: S-EPMC9081176 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature