Research ArticleCancer

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells

See allHide authors and affiliations

Science Translational Medicine  18 Jul 2018:
Vol. 10, Issue 450, eaaq1093
DOI: 10.1126/scitranslmed.aaq1093

An oncogene’s enemy is our friend

Inhibitors of oncogenic kinases such as MEK are becoming increasingly common as an approach to treating cancer, but these drugs’ effectiveness is often short-lived, as tumors develop resistance. Phosphatases, a class of proteins whose activity counteracts that of kinases, are not routinely targeted by cancer therapies but may offer an alternative approach to treatment in some cases. In particular, Kauko et al. determined that the loss of a phosphatase called PP2A can play a major role in resistance to MEK inhibition in lung cancer. The authors also selected a compound that activates PP2A and demonstrated that it can effectively combine with a MEK inhibitor and overcome drug resistance in multiple mouse models of human lung cancer.