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ASCO 2025 | The evolving landscape of targeted therapies for RAS-mutated colorectal cancers
John Strickler, MD, Duke University, Durham, NC, comments on the evolving landscape of targeted therapy for RAS-mutated colorectal cancers, particularly those with historically ‘undruggable’ mutations like KRAS G12D or G12V. Dr Strickler notes that early data from KRAS-specific inhibitors has been promising, but challenges remain, including inherent resistance in colorectal cancer, and that a slower, more nuanced approach may be needed to optimize response and durability. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Well, we’ve already seen now some of these KRAS specific inhibitors, KRAS G12D inhibitors and pan KRAS inhibitors enter the clinic. Most of our early data comes from different tumor types, specifically pancreatic cancer, lung cancer and a smattering of other cancers. We haven’t seen as much data yet specific to colorectal cancer. And I think one of the challenges with colorectal cancer is there appears to be some inherent resistance...
Well, we’ve already seen now some of these KRAS specific inhibitors, KRAS G12D inhibitors and pan KRAS inhibitors enter the clinic. Most of our early data comes from different tumor types, specifically pancreatic cancer, lung cancer and a smattering of other cancers. We haven’t seen as much data yet specific to colorectal cancer. And I think one of the challenges with colorectal cancer is there appears to be some inherent resistance. And we’ve learned these lessons before. We have learned these lessons for BRAF-V600E, and we’ve learned it for KRAS-G12C. And I think what we’re doing increasingly is applying these lessons that we’ve learned from similar targets in the space. So I do think we will eventually bring these therapeutics into colorectal cancer, but it may be a little bit harder, a little bit slower road as we try to determine the optimal pairing of those KRAS inhibitors together with other agents to maximize response and make those responses more durable.
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Disclosures
Stock and Other Ownership Interests – Triumvira Immunologics, Inc
Consulting or Advisory Role – Abbvie; Amgen; Astellas Pharma; AstraZeneca; Bayer; Beigene; Bristol Myers Squibb Foundation; Daiichi Sankyo/Astra Zeneca; GE Healthcare; GlaxoSmithKline; Incyte; Ipsen; Jazz Pharmaceuticals; Johnson & Johnson/Janssen; Leap Therapeutics; Lilly; Merck; Natera (Inst); Pfizer; Quanta Therapeutics; Regeneron; Roche/Genentech; Sanofi; Seagen; Taiho Oncology; Takeda; Xilio Therapeutics
Research Funding – A*STAR (Inst); Abbvie (Inst); Amgen (Inst); Apollo Therapeutics; AstraZeneca/MedImmune (Inst); Bayer (Inst); BeiGene (Inst); Curegenix (Inst); Daiichi Sankyo/Lilly (Inst); Erasca, Inc (Inst); GlaxoSmithKline (Inst); Leap Therapeutics (Inst); Lilly (Inst); Novartis; Pfizer; Quanta Therapeutics (Inst); Revolution Medicines (Inst); Roche/Genentech (Inst)
Expert Testimony – Seagen
