Context dependent isoform specific PI3K inhibition confers drug resistance in hepatocellular carcinoma cells

Background: Targeted therapies for Primary liver cancer (HCC) is limited to the multi-kinase inhibitors, and not fully effective due to the resistance to these agents because of the heterogeneous molecular nature of HCC developed during chronic liver disease stages and cirrhosis. Although combinatorial therapy can increase the efficiency of targeted therapies through synergistic activities, isoform specific effects of the inhibitors are usually ignored. This study concentrated on PI3K/Akt/mTOR pathway and the differential combinatory bioactivities of isoform specific PI3K-alpha inhibitor (PIK-75) or PI3K-beta inhibitor (TGX-221) with Sorafenib dependent on PTEN context.