The Experimental Oncology Group of the Spanish National Cancer Research Center focuses its research on identifying therapeutic strategies against pancreatic and lung tumors induced by the KRAS oncogene. For this purpose, we use genetically modified experimental mouse models that closely reproduce the natural history of the corresponding human tumors. In the case of pancreatic tumors, four years ago we published that deletion by genetic manipulation of two targets involved in signal transmission of the KRAS oncogene, RAF1 kinase and the epithelial growth factor receptor, EGFR, induced complete regression of a percentage of such tumors (Blasco et al., Cancer Cell, 2019. PMID: 30975481).
These studies demonstrated for the first time that it was possible to eliminate pancreatic ductal adenocarcinomas by inhibiting two targets involved in KRAS signaling, although most of the tumors that responded to this therapeutic strategy were smaller tumors. Since then, the work of our laboratory has focused on (i) identify additional targets that, in combination with RAF1 and EGFR deletion, will allow us to achieve the elimination of all, or at least a large majority, of pancreatic tumors induced by the KRAS oncogene regardless of their size or stage without causing significant toxic effects and (ii) in pharmacologically validating these therapeutic strategies by using selective inhibitors against these targets either alone or in combination with the recently identified KRAS inhibitors, with the ultimate goal of being able to transfer these results to cancer patients.