Castration-resistant prostate cancer is resensitized to androgen deprivation by autophagy-dependent apoptosis induced by blocking SKP2.

ABSTRACT: Resistance to androgen receptor (AR)-targeted therapies for prostate cancer (PCa) is characteristic of an aggressive subtype called castration-resistant prostate cancer (CRPC) and is often associated with tumor relapse. Both relapse and poor prognosis in patients with CRPC are associated with increased abundance of the E3 ubiquitin ligase SKP2. Therefore, we investigated the therapeutic potential of combined inhibition of AR and SKP2 for CRPC. We found that combined targeting of AR and SKP2 with small-molecule inhibitors decreased proliferation in two CRPC cell lines in culture and in xenografts in humanized mice. Furthermore, combined therapy in mice markedly decreased the growth of Pten/Trp53 double-knockout tumors, a particularly invasive model of CRPC, whereas disruption of eith

SUBMITTER: Celada SI 

PROVIDER: S-EPMC11784317 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature