Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Barbacid, Mariano
Location Spanish National Cancer Research Center (CNIO)
Primary Field Medical Genetics, Hematology and Oncology
 Election Citation
Barbacid?s main accomplishments include isolation and establishment of the mechanism of activation of the H-Ras human oncogene; demonstration that oncogenes are targets of chemical carcinogens; isolation and functional characterization of the Trk family of neurotrophin receptors; and redefinition of the role of interphase Cdks in the mammalian cell cycle.
 Research Interests
The main research interests of the Barbacid lab is to identify therapeutic strategies to target KRAS mutant tumors which are responsible for over 20% of all human tumors. Given the undruggable nature of KRAS (with the exception of the KRASG12c mutation), we have, during the last decade, deconstructed oncogenic KRAS signaling using a new generation of GEM tumor models of Kras/Tp53 driven lung and pancreatic tumors to identify those effectors whose systemic ablation or inactivation will result in therapeutic responses without inducing unacceptable toxicities. This systematic approach has revealed that most KRAS signaling effectors are not suitable targets due to either lack of therapeutic activity (ARAF, BRAF, CDK2 etc..) or to the induction of unaccepted toxicities (MEK, ERK, CDK1). Only RAF1 and to a lesser extent, CDK4 have turned out to be suitable therapeutic targets. In addition, ablation of EGFR, un upstream effector of KRAS signaling, also resulted in significant therapeutic activity in combination with RAF1 ablation in pancreatic, but not in lung tumors. We are now trying to identify pharmacological approaches that can reproduce these genetic strategies, so our results could be eventually translated to the clinic.

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