Why some EGFR- and KRAS-mutant lung cancers stop responding to targeted medicines
PDX tumor-TME acquired resistance
This project looks at why EGFR- and KRAS-mutant non-small cell lung cancers stop responding to targeted drugs and tries approaches to make treatments work better for those patients.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Francisco NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-11190984 on NIH RePORTER |
What this research studies
Researchers use patient-derived tumor models (PDXs) and organoids from EGFR- and KRAS-mutant lung cancers to study how tumors and the surrounding immune and stromal cells change when drugs stop working. They profile tumors with histology, immunohistochemistry, RNA sequencing, single-cell RNAseq, mass-spectrometry proteomics, and CRISPR-based genetic screens to find molecular and cellular drivers of acquired resistance. The team will test drugs that target specific cells in the tumor microenvironment—for example, therapies aimed at M2 tumor-associated macrophages—to see if combining those agents with targeted inhibitors restores drug response. Findings could guide new combination strategies and identify biomarkers for future clinical trials.
Who could benefit from this research
Good fit: Ideal candidates are people with EGFR- or KRAS-mutant non-small cell lung cancer whose tumors have developed resistance to targeted therapies and who can provide tumor tissue or consider enrollment in related trials.
Not a fit: People without EGFR or KRAS mutations, or whose tumors remain sensitive to targeted therapies, are unlikely to benefit directly from this specific research.
Why it matters
Potential benefit: If successful, this work could lead to new combination treatments or biomarkers that help targeted drugs work again for patients with resistant EGFR- or KRAS-mutant lung cancer.
How similar studies have performed: Using patient-derived models, molecular profiling, and tumor-microenvironment targeting has shown promise in preclinical and early clinical work, but durable solutions for acquired resistance are still limited.
Where this research is happening
San Francisco, United States
- University of California, San Francisco — San Francisco, United States (Active)
Researchers
- Principal investigator: Roth, Jack — University of California, San Francisco
- Study coordinator: Roth, Jack
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.