This technology uses glutaminase inhibition as a therapy for KEAP1/NRF2 dysregulated NSCLC. These inventors identified that mutation of SLC1A5 or GPD2 in combination with KEAP1/NRF2 dysregulation leads to synthetic lethality. This finding led to the observation that KEAP1/NRF2 dysregulation results in dependence on glutamine metabolism, and suggested that inhibition of glutamine metabolism may be a therapeutic target for KEAP1/NRF2 dysregulated NSCLC. In proof of concept experiments, the inventors demonstrated that inhibition of glutaminase, a key enzyme in glutamine metabolism, with the small molecule CB-893 led to significantly increased lifespan and decreased tumor burden in both mouse and human patient-derived-xenograft in vivo models. These findings indicate that glutaminase inhibition is an attractive therapeutic target for KEAP1/NRF2 dysregulated NSCLC, and that KEAP1/NRF2 dysregulation could be used as a theranostic marker to direct NSCLC therapy.