Gina DeNicola, Ph.D.

Changes in the pathways in which cells signal one another are implicated in the development of cancer. One of the most common pathways mutated in lung cancer is called NRF2/KEAP1. In order to understand the role of the NRF2/KEAP1 pathway in cancer development and the emergence of drug resistance, we have generated NRF2 mutant mice to study its function in lung cancer. We will use this model to study the role of NRF2 mutation in both tumor initiation and progression. We will also investigate whether therapy that inhibits NRF2 itself or exploits NRF2 activation would eradicate NRF2 mutant tumors. This could lead to new therapies for the treatment of lung cancer patients with alterations in the NRF2/KEAP1 pathway.

Update: We have generated NRF2 and KEAP1 mutant mouse lung cancer models in order to advance our understanding of the role of NRF2 in lung tumor development and the response of NRF2/KEAP1 mutant tumors to therapy. We are testing the efficacy of NRF2 inhibition in these models, as well as therapies that selectively target cells with high NRF2 activity. By taking two different approaches, we hope to identify the Achilles' heel of NRF2 mutant tumors. Our novel models will accelerate the identification of therapeutic options for these patients.