Blocking SMARCA2 to help SMARCA4‑mutant lung cancers respond to KRAS G12C drugs
Targeting SMARCA2 to overcome resistance of SMARCA4-mutant lung cancer to KRAS G12C inhibitors
['FUNDING_R21'] · UNIVERSITY OF TX MD ANDERSON CAN CTR · NIH-11251746
Seeing whether medicines that remove a protein called SMARCA2 can help people with SMARCA4‑mutant, KRAS G12C lung cancer respond better to KRAS G12C drugs.
Quick facts
| Phase | ['FUNDING_R21'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | UNIVERSITY OF TX MD ANDERSON CAN CTR (nih funded) |
| Locations | 1 site (HOUSTON, UNITED STATES) |
| Trial ID | NIH-11251746 on ClinicalTrials.gov |
What this research studies
Researchers are developing and using PROTAC molecules that selectively degrade SMARCA2 to test whether removing SMARCA2 overcomes resistance in SMARCA4‑mutant, KRAS G12C lung cancer models. The team will combine their lead degrader (YD23) with KRAS G12C inhibitors in laboratory experiments using cancer cell lines and likely animal models, and use assays such as ATAC‑seq to study chromatin and pathway changes. The work is preclinical chemical‑biology and molecular analysis aimed at understanding mechanisms of drug resistance and identifying combination strategies that could be moved toward trials. This project does not itself appear to be a patient treatment trial but could inform future clinical testing for a defined subgroup of lung cancer patients.
Who could benefit from this research
Good fit: The most relevant patients would be people with non‑small cell lung cancer whose tumors have both KRAS G12C mutations and loss or mutation of SMARCA4.
Not a fit: Patients without a KRAS G12C alteration or without SMARCA4 mutation are unlikely to benefit directly from this specific line of research.
Why it matters
Potential benefit: If successful, this approach could lead to new combination treatments that restore or extend responses to KRAS G12C inhibitors for patients whose tumors carry SMARCA4 mutations.
How similar studies have performed: Preclinical studies have suggested SMARCA2 is a vulnerability in SMARCA4‑mutant cancers and KRAS G12C inhibitors are effective but prone to resistance, while combining SMARCA2 degraders with KRAS G12C inhibition is a relatively new and mainly preclinical idea.
Where this research is happening
HOUSTON, UNITED STATES
- UNIVERSITY OF TX MD ANDERSON CAN CTR — HOUSTON, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: LISSANU, YONATHAN — UNIVERSITY OF TX MD ANDERSON CAN CTR
- Study coordinator: LISSANU, YONATHAN
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.