Frequent loss-of-function mutations in KEAP1, a master regulator of the NRF2 antioxidant pathway, accelerate mutant KRAS driven lung carcinogenesis, but also impose a dependency of these tumors on glutaminolysis. Using a precision medicine–based approach, this work uncovers a metabolic vulnerability of KRAS–KEAP1-mutant lung cancers that can be therapeutically exploited using currently available glutaminase inhibitors and provides a scientific rationale for patient selection in clinical trials.
- Rodrigo Romero
- Volkan I Sayin
- Thales Papagiannakopoulos
