Targeting protein-quality control in KRAS-mutant cancers
Proteostasis Reprogramming in Mutant KRAS-Driven Cancers
This project tests whether blocking a protein-stress pathway called IRE1a can help KRAS-targeted drugs work better for people with KRAS-mutant lung and pancreatic cancers.
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-11288770 on NIH RePORTER |
What this research studies
From a patient's viewpoint, researchers are studying why cancers with KRAS mutations become resistant to new KRAS-targeted drugs and are testing a way to stop that resistance. In lab-grown cancer cells and in animal models, they turn off or drug-block a protein-stress pathway (IRE1a) that tumors reactivate when KRAS is inhibited. They combine IRE1a suppression with KRAS inhibitors to see if that leads to stronger and longer-lasting tumor shrinkage. The team is also studying how KRAS signaling keeps IRE1a active so they can find better ways to block the resistance.
Who could benefit from this research
Good fit: People whose tumors carry KRAS mutations—especially KRASG12C-driven non‑small cell lung cancer or KRAS-mutant pancreatic cancer—would be the most relevant candidates for related trials or therapies.
Not a fit: People whose cancers do not have KRAS mutations or whose tumors are driven by unrelated mechanisms are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, this approach could make KRAS-targeted therapies work longer and produce deeper, more durable responses for people with KRAS-mutant cancers.
How similar studies have performed: Preclinical work reported by the team shows promising results in cell and animal models when IRE1a is suppressed alongside KRAS inhibitors, but this combination has not yet been proven in people.
Where this research is happening
Houston, United States
- University of Tx Md Anderson Can Ctr — Houston, United States (Active)
Researchers
- Principal investigator: Chen, Xi — University of Tx Md Anderson Can Ctr
- Study coordinator: Chen, Xi
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.