STK11 mutation + KEAP1 mutation

Here, we identified targeting proximal receptor tyrosine kinase (RTK) signaling using the SOS1 inhibitor (SOS1i) BI-3406 as a strategy to improve responses to G12Ci treatment...Treatment with SOS1i both delayed acquired G12Ci resistance and limited the total number of resistant colonies regardless of KEAP1 and STK11 mutational status. Together, these data suggest that targeting SOS1 could be an effective strategy to both enhance G12Ci efficacy and prevent G12Ci resistance regardless of co-mutations.

ML-based immune phenotyping by spatial distribution of T cells in resected NSCLC is able to identify patients at greater risk of disease recurrence after surgical resection. LUADs with concurrent KEAP1 and STK11 mutations are enriched for altered and desert immune phenotypes.

While both KEAP1 and STK11 mutations are associated with decreased OS in KRAS-mutant LUAD, we find in two independent cohorts that only KEAP1 mutations and KEAP1/STK11 co-mutations, but not STK11 mutations, are associated with metastasis. We also found that FGA, TMB, CDKN2A/B deletions are strongly associated with metastasis. Further research is necessary to understand the influence of KEAP1 mutations, independent of and in-conjunction with STK11 mutations, on metastasis.

In POPLAR and OAK trials, we further made the similar result (P = 0.143) and SMARCA4 mutated patients who receiving chemotherapy had worse survival (P =0.016). In addition, we found that SMARCA4 mutated patients could benefit from immunotherapy with more than 4 months median survival extension compared with chemotherapy, Conclusion SMARCA4 mutated NSCLC patients had worse survival and could not benefit from chemotherapy as well as immunotherapy; however, survival of these patients receiving immunotherapy is better than that receiving chemotherapy