Speaker: Mariano Barbacid, PhD - AXA-CNIO Professor of Molecular Oncology - Centro Nacional de Investigaciones Oncológicas (CNIO) - Spanish National Cancer Research Center - Madrid, Spain
Presentation
Speaker: Mariano Barbacid, PhD - AXA-CNIO Professor of Molecular Oncology - Centro Nacional de Investigaciones Oncológicas (CNIO) - Spanish National Cancer Research Center - Madrid, Spain
Date: Friday 10 June 2022, 12PM
Place: Auditorium
Host: Dr. Cristina Mayor-Ruiz, Junior Group Leader - Targeted protein degradation and drug discovery Lab. - IRB Barcelona - Mechanisms of Disease Programme.
ABSTRACT:
KRAS, an oncogene responsible for one fourth of all human cancers, was discovered four decades ago. Yet, the first selective inhibitor was not approved until 2021. In spite of this long-awaited breakthrough, current KRAS inhibitors only block one of the multiple oncogenic isoforms, KRASG12C which is primarily present in lung adenocarcinomas. Moreover, tumor resistance to KRAS inhibitors appears to be a significant issue in the clinic (Awad et al., N Engl J Med, 2021; Zhao et al., Nature 2021). In an effort to provide experimental information that might help to improve current KRAS targeting strategies, we have generated two genetically engineered mouse models of Kras/Trp53-driven lung adenocarcinoma to (i) interrogate the mechanisms of drug resistance that appear in KRASG12C driven tumors and (ii) compare the therapeutic consequences of eliminating instead of inhibiting KRAS oncoproteins. Our results indicate that Kras gene amplification along with activation of drug metabolic pathways are major components of the mechanisms responsible for the acquisition of resistance. More importantly, genetic evidence strongly supports the concept that Kras ablation provides superior therapeutic benefits than Kras inhibition, thus arguing for the development of Kras degron strategies.
Organizer: IRB Barcelona
IMPORTANT: For attendees outside the PCB community you must register at least 24h before the seminar.
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