Specific co-mutations in KRAS-mutant NSCLC improve treatment response
MD Anderson Research Highlight July 10, 2025
Patients with KRAS-mutant non-small cell lung cancer (NSCLC) also often have co-mutations in KEAP1 and LKB1, which are associated with problems with DNA damage repair pathways, treatment resistance and reduced survival. Targeting the two main components in the DNA damage repair pathway using ATR inhibitors has emerged as a therapeutic strategy, but there currently are no biomarkers to determine which patients with NSCLC are likely to benefit. To provide insights, researchers led by , examined the role of KEAP1 and LKB1 co-mutations on ATR inhibitor response in NSCLC tumors. These co-mutations were associated with enhanced response to ATR inhibitors both in vitro and in vivo. Moreover, adding immune checkpoint blockade or chemotherapy in combination with ATR inhibitors further improved antitumor activity. These results suggest that these co-mutations could be potential predictive biomarkers for ATR inhibitor response in patients with NSCLC. Learn more in .
These results provide invaluable insights so that we may better identify KRAS-mutant NSCLC patients most likely to respond to combination treatment with ATR inhibitors in order to lower their tumor burden and improve overall outcomes. Since patients with these mutations are usually resistant to standard immunotherapy, these findings may offer another potential treatment option if ongoing studies confirm the benefits we observed.