KRAS oncogene copy numbers regulate lung tumor formation and response to therapy
Centro de Investigación del Cáncer (CSIC-Universidad de Salamanca), Salamanca.
KRAS oncogenes have been identified in a quarter of all human lung tumors. Recently, several inhibitors were developed that target specific mutant KRAS isoforms and two of them, directed against the KRAS G12C oncoprotein, have just been approved. However, most patients develop resistance against these inhibitors and no actual survival benefits have been observed in clinical trials. Thus, indicating that a better understanding of the mechanisms of tumor formation and response to KRAS inhibitors is necessary to develop more efficacious therapeutic strategies. In this presentation, I will discuss what we have learned from genetically engineered mouse models about the mechanisms of lung tumor formation and the development of resistance to KRAS inhibition as a consequence of KRAS copy number variations.