Turning on immune signals to fight KRAS lung cancer
Targeting the cytokine circuitry of KRAS driven lung cancer
['FUNDING_R01'] · DANA-FARBER CANCER INST · NIH-11295901
This work tries to boost innate immune signaling to help KRAS-mutant lung cancers, especially those with LKB1 loss, respond better to immunotherapy.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | DANA-FARBER CANCER INST (nih funded) |
| Locations | 1 site (BOSTON, UNITED STATES) |
| Trial ID | NIH-11295901 on ClinicalTrials.gov |
What this research studies
This project focuses on KRAS-mutant lung cancer, particularly tumors that have lost the LKB1 (STK11) tumor suppressor. Researchers are studying how disrupted cytokine and innate immune signaling—including silencing of the STING pathway—allows these cancers to evade the immune system. They aim to block the DNA exonuclease TREX1 to reactivate the cGAS-STING-STAT1 immune pathway and test whether this makes tumors more sensitive to PD-1 immunotherapy and to natural killer (NK) cell killing in lab and animal models. The goal is to identify drug strategies and biomarkers that could be moved into clinical testing for this aggressive subtype.
Who could benefit from this research
Good fit: People with advanced non-small cell lung cancer whose tumors carry KRAS mutations, particularly those with STK11/LKB1 loss, would be the most relevant candidates.
Not a fit: Patients whose tumors do not have KRAS mutations or LKB1/STK11 loss, or patients with other cancer types, are unlikely to benefit directly from this work.
Why it matters
Potential benefit: If successful, this approach could make some KRAS-LKB1 lung cancers respond to existing immunotherapies and enable new combination treatments.
How similar studies have performed: Preclinical studies, including work by this team, have shown that activating cGAS-STING or inhibiting TREX1 can restore immune responses and improve PD-1 sensitivity in models, but clinical proof in patients is not yet established.
Where this research is happening
BOSTON, UNITED STATES
- DANA-FARBER CANCER INST — BOSTON, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: BARBIE, DAVID A — DANA-FARBER CANCER INST
- Study coordinator: BARBIE, DAVID A
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.
Conditions: Cancer Genes, Cancer-Promoting Gene, Cancers