Mariano Barbacid
Spanish National Cancer Research Center (CNIO)
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
International Member
(elected 2012)
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Biosketch
Mariano Barbacid got his Ph.D. in Madrid (1974) and trained as a postdoctoral fellow at the US National Cancer Institute. In 1978 he started his own research group to study the molecular events responsible for the development of human tumors, leading to the isolation of the first human oncogene, H-RAS, in 1982. In 1988, he joined Bristol Myers-Squibb where he became Vice President, Oncology Drug Discovery. In 1998, he returned to Madrid to create and direct the Spanish National Cancer Research Center (CNIO). In 2011 he stepped down as Director to concentrate on his own research as Head of the Experimental Oncology Group. In 2012, he was inducted to the US National Academy of Sciences US and in 2014, elected Fellow of the AACR Academy. His work has been recognized by several international awards including the Steiner Prize (Bern, 1988), the Ipsen Prize (Paris, 1994), the Brupbaher Cancer Research Prize (Zurich, 2005), the Medal of Honor of the IACR (Lyon, 2007) and the Burkitt Medal (Dublin, 2017). He is a recipient of an Endowed Chair from the AXA Research Fund (Paris). To date, he has authored 320 publications, including 239 original research articles. His current “h” factor is 117.
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.
