Noel Warfel, Ph.D.
University of Arizona
Funded by LUNG FORCE
Blocking Enzyme PIM Kinase to Treat Non-Small Cell Lung Cancer
Non-small cell lung cancers (NSCLC) rapidly become resistant to therapy. Nrf2 is a gene that contributes to NSCLC progression and the onset of resistance to therapy. The protein KEAP1 keeps Nrf2 levels low, but in more than half of NSCLCs, mutations disrupt the function of KEAP1. Nrf2 activation represents a promising target for therapy. We recently discovered that enzymes called PIM kinases control the activation of Nrf2. PIM inhibitors can block Nrf2 activity independent of KEAP1. The goal of this research is to determine how PIM inhibitors inactivate Nrf2 in KEAP1-mutant tumors and to test the efficacy of PIM inhibitors in combination with currently approved therapies in NSCLC. PIM inhibitors have entered clinical trial testing and our findings could quickly impact patient care.