Preventing resistance to KRAS-targeted treatments in colorectal cancer
Overcoming adaptive feedback resistance to KRAS inhibition in colorectal cancer
Researchers are combining drugs to help people with KRAS-mutant colorectal cancer respond better and longer to new KRAS-targeted therapies.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Massachusetts General Hospital NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11306623 on NIH RePORTER |
What this research studies
At Massachusetts General Hospital, the team is studying why colorectal tumors rapidly reactivate the KRAS pathway and stop KRAS inhibitors from working. They analyze tumor samples and lab models to map the adaptive feedback signals that drive resistance. The researchers test combinations of drugs (for example adding EGFR-targeting agents) in cell and preclinical models to find strategies that block pathway reactivation. Promising combinations will be prioritized to inform future clinical trials for patients.
Who could benefit from this research
Good fit: Ideal candidates are people with colorectal cancer whose tumors have KRAS mutations (such as G12C or G12D) and who are candidates for KRAS-targeted therapies or future combination trials.
Not a fit: Patients without KRAS-mutant tumors or whose cancers rely on different resistance pathways may not benefit from these specific combination approaches.
Why it matters
Potential benefit: Could lead to combination treatments that make KRAS-targeted drugs more effective and durable for colorectal cancer patients.
How similar studies have performed: Previous work showed combination approaches (for example adding EGFR blockade) improved outcomes in BRAF-mutant colorectal cancer, and KRASG12C inhibitors have strong responses in lung cancer but limited and less durable responses so far in colorectal cancer, so this approach has supportive precedent but remains unproven for KRAS-mutant CRC.
Where this research is happening
Boston, United States
- Massachusetts General Hospital — Boston, United States (Active)
Researchers
- Principal investigator: Corcoran, Ryan Bruce — Massachusetts General Hospital
- Study coordinator: Corcoran, Ryan Bruce
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.