Why some colorectal cancers resist KRAS-targeted drugs
Understanding intrinsic resistance to direct KRAS inhibition in colorectal cancers
This project tests whether blocking specific signaling enzymes can help KRAS-targeted drugs work better for people with KRAS-mutant colorectal cancer.
Quick facts
| Grant type | R37 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Francisco NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-11241997 on NIH RePORTER |
What this research studies
Researchers are looking inside colorectal tumor cells to find why KRAS-targeting drugs often fail in this cancer type. They map how proteins change when KRASG12C is blocked and use a broad kinase knockdown approach to find enzymes that link KRAS to CTNNB1 (beta‑catenin) activity. The team then checks whether blocking those enzymes together with KRAS inhibitors lowers CTNNB1-driven tumor signals without causing widespread toxicity. Most work is done in lab-grown cancer cells and preclinical models to identify combinations worth testing in patients later.
Who could benefit from this research
Good fit: People with metastatic colorectal cancer whose tumors carry the KRASG12C mutation and show high CTNNB1 (beta‑catenin) activity would be the most relevant candidates for follow-up clinical trials.
Not a fit: Patients whose tumors lack KRAS mutations or who have resistance driven by other pathways likely would not benefit from these specific combinations.
Why it matters
Potential benefit: If successful, this work could lead to new drug combinations that make KRAS-targeted therapies effective for more people with colorectal cancer.
How similar studies have performed: KRASG12C inhibitors have improved outcomes in lung cancer but have only shown limited impact in colorectal cancer, and combining KRAS blockade with other pathway inhibitors is an emerging approach with mixed early results.
Where this research is happening
San Francisco, United States
- University of California, San Francisco — San Francisco, United States (Active)
Researchers
- Principal investigator: Gordan, John D — University of California, San Francisco
- Study coordinator: Gordan, John D
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.