RM-029

To investigate this, we developed a preclinical model that mimics the development of resistance to KRAS-G12C inhibitors (G12Ci), such as adagrasib and RMC-4998...Mechanistically, these combination therapies led to profound remodeling of the tumor immune microenvironment, making it less immunosuppressive, and promoted cancer cell death that primed an immune response, with an influx of cytotoxic T lymphocytes recognizing tumor associated antigens shared between G12Ci resistant and sensitive cancer cells. Promotion of immune-mediated bystander elimination of drug-resistant cells may provide a paradigm for tackling the problem of drug resistance in cancer more broadly.