Once labeled “undruggable,” KRAS has emerged as one of oncology’s most promising—yet complex—targets. With nearly 90% of pancreatic cancers and 30-40% of lung and colorectal cancers harboring KRAS mutations, the need for effective therapies is urgent. Recent FDA approvals of KRAS G12C inhibitors have signaled a new era, but the rise of resistance and diverse mutation profiles demand deeper innovation. As preclinical tools and combination strategies evolve, scientists must ask: how do we stay ahead of KRAS-driven resistance and translate insights into patient-specific treatment success?

So, what will it take to overcome the final barriers to fully unlocking the therapeutic potential of KRAS?

In this episode of Crowncast, host Jonny McMichael, VP of Client Experience & Enablement at Crown BioScience, is joined by Dr. Rajendra “Jen” Kumari, Executive Director of Integrated Solutions. Together, they delve into KRAS biology, resistance mechanisms, and preclinical strategies reshaping drug discovery. Their conversation touches on cutting-edge translational modeling and what the future holds for combination therapies targeting KRAS mutations.

Key topics covered in this episode:

Why KRAS mutations are uniquely challenging—and how recent breakthroughs have shifted the “undruggable” narrative.

The rise of G12C inhibitors and how resistance is reshaping combination strategies in colorectal and lung cancer.

The essential role of preclinical models, including engineered systems and PDXs, in predicting clinical response and guiding next-gen drug development.

About the Guest:

Dr. Rajendra Kumari brings over two decades of oncology research experience to Crown BioScience. A PhD in pharmacology from the University of Leicester, Jen co-founded preclinical CRO PreCOS in 2010, which was acquired by Crown in 2013. She has held various leadership roles including CSO, COO, and GM of Crown UK, and now leads global integrated solutions, driving innovation in translational modeling and oncology strategy.