Trastuzumab Deruxtecan Combination Strongly Enhances Responses and Overcomes Sotorasib Resistance in -Mutant NSCLC.

Introduction: Recent advances in the treatment of -mutant non-small cell lung cancer (NSCLC) have led to the development of KRAS inhibitors, such as sotorasib and adagrasib. However, resistance and disease progression remain significant challenges. In this study, we investigated the therapeutic potential of combining trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody-drug conjugate, with sotorasib in -mutant NSCLC, while also evaluating HER2 expression in NSCLC samples.

Peristromal niches protect lung cancers from targeted therapies through a combined effect of multiple molecular mediators.

Targeted therapies directed against oncogenic signaling addictions, such as inhibitors of ALK in ALK+ NSCLC often induce strong and durable clinical responses. However, they are not curative in metastatic cancers, as some tumor cells persist through therapy, eventually developing resistance. Therapy sensitivity can reflect not only cell-intrinsic mechanisms but also inputs from stromal microenvironment.