Targeted K-Ras(G12C) therapy that degrades the mutant protein and releases local chemotherapy
Official title: Proximity-triggered, mutant-specific modification of K-Ras(G12C) with local polypharmaceutical release
Funded at Cold Spring Harbor Laboratory · NIH-11270832 · Data updated 2026-11-12
A new targeted treatment aims to tag and degrade the K‑Ras(G12C) cancer protein while releasing chemotherapy agents directly inside tumors for people whose cancers carry the K‑Ras(G12C) mutation.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Cold Spring Harbor Laboratory NIH-funded |
| Lab location | 1 site (Cold Spring Harbor, United States) |
| Project start | February 3, 2025 |
| Project end | January 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $224,400 |
| NIH project number | 5R21CA296712-02 |
| Project ID | NIH-11270832 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with tumors confirmed to carry the K‑Ras(G12C) mutation (for example certain non-small cell lung and colorectal cancers) and who are eligible for early-phase experimental treatments would be ideal candidates.
✕Less likely to help
Patients whose tumors do not carry the K‑Ras(G12C) mutation or who are unable to join experimental trials would not be expected to benefit from this approach.
What this research studies
If your tumor has the K‑Ras(G12C) mutation, this project develops single molecules (prodrugs) that bind the mutant protein and transfer chemical fragments to cysteine 12. Those fragments are designed to recruit the cell's E3 ligase machinery to mark K‑Ras(G12C) for degradation while the prodrug also releases jerantinine alkaloids that kill cancer cells through multiple mechanisms. Because the drug is proximity-triggered and releases chemotherapy locally, the approach aims to hit several cancer pathways at once with less systemic exposure. This work is currently preclinical lab-based chemistry and cell/animal testing and would require clinical trials before patients could receive the therapy.
Why it matters
Potential benefit: Could provide a single, mutation-specific therapy that both destroys the mutant K‑Ras protein and delivers potent chemotherapy inside tumors, potentially improving responses and lowering systemic side effects.
How similar studies have gone: Covalent K‑Ras(G12C) inhibitors (sotorasib, adagrasib) have benefited some patients but resistance and limited durability are common, and the proposed prodrug-plus-degrader approach is novel and unproven in humans.
Where this research is happening
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Cold Spring Harbor Laboratory
Cold Spring Harbor, United States Active
Researchers
- Principal investigator: Moses, John Edward — Cold Spring Harbor Laboratory
- Study coordinator: Moses, John Edward
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.