Galan-Cobo et al. show this disruption compensatorily engages ATR–CHK1, creating sensitivity to ATR inhibitors; in KEAP1 and/or LKB1-deficient NSCLC models, ceralasertib was strongly active, synergized with gemcitabine, and enhanced anti-tumor immunity. The gene discussed is STK11; the disease is non-small cell lung carcinoma.