Overcoming adaptive resistance to KRASG12D blockade in pancreatic cancer through vertical pathway inhibition
In PDAC, adaptive RAS-MAPK reactivation following KRASG12D inhibition can be mediated by different RTKs and influenced by cell state. Combinations of mutant-selective KRASi and RAS(ON) multi-selective inhibitors may represent a promising universal strategy to surmount adaptive resistance in PDAC patients.
Authors
- Jakob M. Riedl (ORCID: https://orcid.org/0000-0002-5144-4715)
- H. John Barnes
- Parasvi S. Patel (ORCID: https://orcid.org/0000-0002-0326-7902)
- Ryan Bruce Corcoran (ORCID: https://orcid.org/0000-0001-8173-5778)
- Jacquelyn Curtis
- Qingxiang Lin (ORCID: https://orcid.org/0000-0002-1496-4180)
- Andrew Scott Liss (ORCID: https://orcid.org/0000-0002-4040-9172)
- Alvin A. Morales-Giron (ORCID: https://orcid.org/0009-0006-0534-2634)
- Hiroyuki Matsubara (ORCID: https://orcid.org/0000-0002-9279-5458)
- Conrad Sander
- Hajime Nakamura
- Ferran Fece de la Cruz
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- Massachusetts General Hospital (US)
- Center for Cancer Research (US)
- Kyoto University Hospital (JP)
Publication Details
- Journal
- Clinical Cancer Research
- Published
- 2026-03-09
- DOI
- https://doi.org/10.1158/1078-0432.ccr-25-1788
- Primary Topic
- Protein Kinase Regulation and GTPase Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00