How HER2-mutant lung cancers respond or become resistant to HER2-targeted medicines
Deciphering the structural determinants of response and resistance to HER2-targeted antibody-drug conjugates and tyrosine kinase inhibitors for HER2-mutant Non-Small Cell Lung Cancer
This project looks at how different HER2 mutations in non-small cell lung cancer change responses to HER2-targeted antibody-drug conjugates and kinase inhibitors to help guide better treatment choices.
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-11306087 on NIH RePORTER |
What this research studies
Researchers will analyze the three-dimensional shapes of different HER2 mutations to see how those changes affect binding and response to HER2-targeted antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs). They will use laboratory models and molecular experiments to recreate resistance that tumors acquire, including additional HER2 mutations and resistance to the ADC’s chemotherapy payload. The team will compare patterns across many recurrent HER2 mutations to find which drugs are more likely to work for specific mutation types. Findings may be linked back to patient tumor samples to help guide future treatment matching and clinical trials.
Who could benefit from this research
Good fit: Patients with non-small cell lung cancer whose tumors have activating HER2 mutations (including exon 20 and other recurrent HER2 mutations) are the most relevant candidates.
Not a fit: People whose tumors lack activating HER2 mutations or who only have HER2 amplification without activating mutations may not benefit directly from this work.
Why it matters
Potential benefit: If successful, this work could help doctors choose the HER2-targeted drug most likely to work for a given HER2 mutation and suggest ways to overcome resistance.
How similar studies have performed: HER2-directed ADCs like trastuzumab deruxtecan have shown clinical benefit in HER2-mutant lung cancer, but systematically linking many specific mutations to optimal drugs and resistance mechanisms is still relatively novel.
Where this research is happening
Houston, United States
- University of Tx Md Anderson Can Ctr — Houston, United States (Active)
Researchers
- Principal investigator: Heymach, John V. — University of Tx Md Anderson Can Ctr
- Study coordinator: Heymach, John V.
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.