KRAS is one of the most frequently mutated oncogenes in human cancer. Despite more than three decades of research, indirect approaches targeting KRAS-mutant cancers have largely failed to show clinical benefit, and direct approaches have been stymied by the apparently ‘undruggable’ nature of KRAS.
Join Brian Lanman of Amgen as he outlines the strategies used to overcome these challenges, the screening approaches employed to identify starting points for these efforts, and the optimization challenges overcome in the identification sotorasib, the first direct KRAS G12C therapeutic to enter human clinical testing.
What You Will Learn
- Why identifying a direct inhibitor of KRAS has proven so challenging
- How covalent inhibition helped to turn KRAS G12C into a tractable target
- What hurdles were overcome in turning initial KRAS G12C binders into potential human therapeutics
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