Effects of KRAS targeted therapies in combination with SHP2 inhbitors or anti-PD-1 on drug-resistant subpopulations.
We investigate how to combat G12Ci-resistant subpopulations in solid tumors by engaging an anti-tumor immune response. We mimic the development of drug resistance by combining traced isogenic KRAS G12C- and G12D-mutant lung cancer cells, where the KRAS G12D mutant cells are inherently resistant to G12Ci. By alleviating RAS-driven immune suppression and potentially inducing immunogenic cell death of G12Ci-responsive cells, we aim to further potentiate an adaptive immune response targeting the drug-resistant population.   We aim to investigate how the active-state KRAS G12C inhibitor RMC-4998, either as monotherapy or in combination with the SHP2 inhibitor (RMC-4550) or anti-PD-1, influences the cancer cell states in the inhibitor-resistant subpopulation of KRAS G12D mutant tumour cells.
We investigate how to combat G12Ci-resistant subpopulations in solid tumors by engaging an anti-tumor immune response. We mimic the development of drug resistance by combining traced isogenic KRAS G12C- and G12D-mutant lung cancer cells, where the KRAS G12D mutant cells are inherently resistant to G12Ci. By alleviating RAS-driven immune suppression and potentially inducing immunogenic cell death of G12Ci-responsive cells, we aim to further potentiate an adaptive immune response targeting the drug-resistant population.   We aim to investigate how the active-state KRAS G12C inhibitor RMC-4998, either as monotherapy or in combination with the SHP2 inhibitor (RMC-4550) or anti-PD-1, influences the cancer cell states in the inhibitor-resistant subpopulation of KRAS G12D mutant tumour cells.
FRANCIS CRICK INSTITUTE