Resistance Mechanisms and Future Directions in HER2-Mutated NSCLC

The discussion turns to mechanisms of resistance to HER2-targeted therapies and the implications for future research and clinical practice. Drs. Santos and Lopes note that, as with other targeted therapies, resistance inevitably develops, necessitating ongoing innovation.

Potential resistance mechanisms include secondary HER2 alterations, activation of bypass signaling pathways, and tumor heterogeneity. The speakers emphasize the importance of repeat molecular profiling at progression to inform subsequent treatment decisions.

Emerging strategies to overcome resistance, including next-generation HER2 inhibitors, combination therapies, and novel ADC constructs were discussed. These approaches aim to enhance durability of response and address unmet clinical needs.

Resistance is a central challenge but also a driver of innovation, with ongoing clinical trials poised to further expand therapeutic options.