Synthetic Lethality in PTEN-Mutant Prostate Cancer Is Induced by Combinatorial PI3K/Akt and BCL-XL Inhibition

Abstract

Synthetic lethality in PTEN-mutant prostate cancer cells with combined PI3K/Akt and BCL-X_L inhibition. PTEN-mutant prostate cancer cells expressing ITGA5 bind to fibronectin in the putative bone marrow niche and transduce survival signals to BCL-X_L Additional PTEN-regulated signals independent of the PI3K/Akt pathway likely feed into the BCL-X_L-regulated survival program to explain synthetic lethality observed with the combination.Visual Overview: http://mcr.aacrjournals.org/content/early/2016/12/02/1541-7786.MCR-16-0202/F1.large.jpg. Mol Cancer Res; 14(12); 1176-81. ©2016 AACR.