Exploiting Dependencies Created by KEAP1/NFE2L2 Mutations in NSCLC to Overcome Radiation Resistance
Radiation plays a crucial role in the treatment of lung cancer, which is the leading cause of cancer-related deaths globally. However, tumors with certain mutations do not respond as well to radiation therapy. We are particularly interested in a pathway called KEAP1/NFE2L2 that may be mutated in non-small cell lung cancers that resist radiation. While the role KEAP1/NFE2L2 plays in radiation resistance is established, previous efforts to develop drugs that target this pathway have not been successful in clinics. We believe treatment of related factors within tumors, especially those that correct errors in DNA, can make these tumors more sensitive to radiation. We will study cancer cell models and use advanced genetic techniques to discover new strategies and targets for selectively interfering with how these mutant cells in lung cancers survive radiation. This may lead to novel strategies to improve outcomes for patients grappling with tumors with these mutations.
