DIRAS3, a natural protein, breaks up mutant KRAS clusters to boost cell recycling and help autophagy-blocking drugs work better
DIRAS3 disrupts K-RAS clustering and signaling, enhancing autophagy and response to autophagy inhibition
Looking at whether restoring DIRAS3 can break apart mutant KRAS in cancers like pancreatic and low-grade serous ovarian cancer so that autophagy-blocking treatments work better.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Tx Md Anderson Can Ctr NIH-funded |
| Lab location | 1 site (Houston, United States) |
| Project ID | NIH-11167446 on NIH RePORTER |
What this research studies
Researchers are studying DIRAS3, a protein that is often low in some KRAS-driven cancers, to see how it changes KRAS behavior at the cell membrane. In lab models they restore DIRAS3 to watch whether it disperses KRAS clusters, increases autophagy, and makes tumors more sensitive to drugs that block autophagy. The work uses cancer cell lines and model systems relevant to pancreatic ductal adenocarcinoma and low-grade serous ovarian cancer to define the mechanisms and treatment combinations. Findings aim to guide future clinical strategies combining DIRAS3-based approaches with autophagy inhibitors.
Who could benefit from this research
Good fit: Patients whose tumors are driven by mutant KRAS—for example certain pancreatic ductal adenocarcinomas or low-grade serous ovarian cancers—would be the main candidates for related future treatments or trials.
Not a fit: Patients whose cancers do not have KRAS mutations or who rely on unrelated tumor pathways are unlikely to benefit from DIRAS3-targeted approaches.
Why it matters
Potential benefit: If successful, this approach could make some KRAS-mutant cancers more responsive to therapies, potentially slowing tumor growth and improving patient outcomes when combined with autophagy inhibitors.
How similar studies have performed: Prior work shows that blocking RAS signaling can induce autophagy and sometimes sensitize tumors to autophagy inhibitors, but using DIRAS3 to disrupt KRAS clustering is a relatively new strategy.
Where this research is happening
Houston, United States
- University of Tx Md Anderson Can Ctr — Houston, United States (Active)
Researchers
- Principal investigator: Bast, Robert C — University of Tx Md Anderson Can Ctr
- Study coordinator: Bast, Robert C
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.