Mechanisms of KRAS signaling in lung cancer development
Dr. Mattias Drösten
Centro Nacional de Investigaciones Oncológicas CNIO
KRAS oncogenes have been identified in a quarter of all human lung tumors. Yet, no selective therapy has been approved to treat KRAS-mutant tumors, although a subset of patients carrying the G12C mutation in KRAS may benefit from the recent development of KRASG12C inhibitors. However, since resistance to these inhibitors will likely occur and patients carrying other mutations in KRAS will not benefit from these developments, it is urgently required to identify novel therapeutic options applicable to most if not all patients with KRAS-mutant tumors. Here I will present novel insights into the mechanisms of KRAS signaling in lung cancer development from genetically engineered mouse models that may help to overcome resistance to targeting either KRAS by itself or its MAPK effector pathway. In the second part of the presentation, I will also discuss recent results exploring the roles of the two KRAS isoforms, KRAS4A and KRAS4B, in lung cancer.