MET-Driven Resistance to Sotorasib in KRAS G12C–Mutant NSCLC and Response to Combined KRAS and MET Inhibition
This study provides real-world evidence that <i>MET</i> amplification is an acquired and potentially targetable resistance mechanism to KRAS G12C inhibition in NSCLC. Our findings support rebiopsy at progression on sotorasib. Further prospective trials are warranted to validate <i>MET</i> amplification as a resistance mechanism and to define optimal therapeutic thresholds for combined KRAS and MET inhibition.
Authors
- Jana Fassunke (ORCID: https://orcid.org/0000-0002-8391-5577)
- Reinhard Büttner (ORCID: https://orcid.org/0000-0001-8806-4786)
- Anna Eisert (ORCID: https://orcid.org/0000-0002-3398-5702)
- Rieke Nila Fischer (ORCID: https://orcid.org/0000-0002-9196-1864)
- Emanuel Niesen
- Heather Scharpenseel
- Juergen Wolf (ORCID: https://orcid.org/0000-0001-8833-8812)
- Carolin Jakob (ORCID: https://orcid.org/0009-0008-5641-6888)
- Sebastian Yves Friedrich Michels (ORCID: https://orcid.org/0000-0003-3164-870X)
- Janna Siemanowski (ORCID: https://orcid.org/0000-0003-2581-1320)
- Malte Verheyen (ORCID: https://orcid.org/0009-0008-7552-9044)
- Matthias Scheffler (ORCID: https://orcid.org/0000-0002-9031-1368)
- Udo Siebolts (ORCID: https://orcid.org/0000-0002-7463-9195)
- Richard F. Riedel (ORCID: https://orcid.org/0000-0002-8883-1188)
- Lucia Nogová (ORCID: https://orcid.org/0000-0002-4502-1812)
- Lea Ruge (ORCID: https://orcid.org/0000-0003-3390-0411)
- Sabine Merkelbach‐Bruse (ORCID: https://orcid.org/0000-0002-0312-5760)
- Carina Heydt (ORCID: https://orcid.org/0000-0003-3184-9579)
- Anne Bunck
- Felix John (ORCID: https://orcid.org/0000-0002-0616-3391)
Institutions
- University of Cologne (DE)
- University Hospital Cologne (DE)
Publication Details
- Journal
- JTO Clinical and Research Reports
- Published
- 2025-10-28
- DOI
- https://doi.org/10.1016/j.jtocrr.2025.100925
- Citations
- 1
- Primary Topic
- Liver physiology and pathology
- Type
- article
- Field-Weighted Citation Impact
- 1.32
Funders
- Amgen
- Eli Lilly and Company
- Pfizer
- Sanofi
- Regeneron Pharmaceuticals
- BeiGene
- Daiichi-Sankyo
- European Society for Medical Oncology
- Siemens Healthineers
- Chugai Pharmaceutical