Overcoming KRAS Drug Resistance with Targeted KRAS-G12V and TEAD Chimeras
Official title: Overcoming Adaptive KRAS Inhibitor Resistance with Ligand-Directed KRAS G12V-panTEAD Chimeras
Funded at Enfuego Therapeutics INC. · NIH-11407293 · Data updated 2026-11-12
This grant aims to develop a targeted approach to treat KRAS-driven cancers by combining mutant KRAS targeting with TEAD pathway engagement to overcome resistance.
Quick facts
| Grant type | Sbir 2 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Enfuego Therapeutics INC. NIH-funded |
| Lab location | 1 site (Pittsboro, United States) |
| Project start | September 14, 2026 |
| Project end | August 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $311,734 |
| NIH project number | 1R44CA314597-01 |
| Project ID | NIH-11407293 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients whose tumors harbor KRAS mutations, particularly G12V, may be eligible in future translational steps or related studies once progressed to clinical testing.
✕Less likely to help
Patients without KRAS mutations or with non-targetable tumors may not benefit from this specific approach.
What this research studies
KRAS-driven cancers are among the deadliest, and current drugs often fail due to resistance. This project proposes a novel RNAi-based strategy to silence mutant KRAS while engaging TEAD-related pathways to block tumor growth. Researchers will design ligand-directed KRAS G12V chimeras that can selectively silence cancer-causing transcripts and potentially curb resistant signaling. The work will involve preclinical studies to test efficacy and safety in relevant models, with an eye toward future clinical translation. If successful, this approach could offer a new avenue for patients whose tumors harbor KRAS mutations.
Why it matters
Potential benefit: Could provide a new, targeted therapy for patients with KRAS-mutant cancers, potentially delaying progression and improving survival if the approach translates to the clinic.
How similar studies have gone: Prior work suggests combining KRAS-targeting strategies with pathway modulators can be synergistic, but this exact KRAS G12V-TEAD chimera approach is innovative and yet to be proven in humans.
Where this research is happening
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Enfuego Therapeutics INC.
Pittsboro, United States Active
Researchers
- Principal investigator: Stanland, Lyla — Enfuego Therapeutics INC.
- Study coordinator: Stanland, Lyla
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.