Targeting specific lung cancers with KRAS and KEAP1 mutations
Synthetic lethal targeting of KRAS/KEAP1 co-mutant non-small cell lung cancer
This work explores new ways to treat a challenging type of non-small cell lung cancer that has both KRAS and KEAP1 gene changes.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Rush University Medical Center NIH-funded |
| Lab location | 1 site (Chicago, United States) |
| Project ID | NIH-11131219 on NIH RePORTER |
What this research studies
We are looking into a specific type of non-small cell lung cancer that has two particular gene changes, KRAS and KEAP1, which often make it hard to treat. Our findings suggest that these cancer cells rely heavily on a protein called HDAC4 for their survival. We are testing a drug, LMK235, that blocks HDAC4 and HDAC5, which appears to be effective against these co-mutant cells but not against other lung cancer cells. We also found that combining LMK235 with an existing FDA-approved drug, AMG510, could work even better for patients with KRAS G12C/KEAP1 co-mutant tumors.
Who could benefit from this research
Good fit: This research is focused on patients with non-small cell lung cancer who have specific KRAS and KEAP1 gene mutations.
Not a fit: Patients whose lung cancer does not have both KRAS and KEAP1 mutations may not directly benefit from this specific approach.
Why it matters
Potential benefit: If successful, this work could lead to more effective treatment options for patients with non-small cell lung cancer that has both KRAS and KEAP1 mutations, especially those resistant to current therapies.
How similar studies have performed: This approach builds on initial findings that identified HDAC4 as a vulnerability in these specific cancer cells, and explores a novel drug combination.
Where this research is happening
Chicago, United States
- Rush University Medical Center — Chicago, United States (Active)
Researchers
- Principal investigator: Maki, Carl G — Rush University Medical Center
- Study coordinator: Maki, Carl G
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.