Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs
Our findings reveal that using metformin for head and neck cancer chemoprevention leads to compensatory activation of a PKA-driven resistance mechanism that can be blocked by cotreatment with NSAIDs. These findings provide a rationale for combining metformin with NSAIDs as a precision head and neck cancer chemoprevention strategy.
Authors
- Ezra E.W. Cohen (ORCID: https://orcid.org/0000-0002-9872-6242)
- Sendi Rafael Adame-Garcia (ORCID: https://orcid.org/0000-0002-5665-8333)
- Thomas S. Hoang (ORCID: https://orcid.org/0000-0003-1282-734X)
- Kuniaki Sato (ORCID: https://orcid.org/0000-0001-6014-1911)
- Paola Y. Anguiano Quiroz (ORCID: https://orcid.org/0000-0002-7317-2191)
- Pham Thuy Tien Vo (ORCID: https://orcid.org/0000-0001-5760-8461)
- Sydney I. Ramirez (ORCID: https://orcid.org/0000-0002-7166-5195)
- Amaya N. Mendez-Molina (ORCID: https://orcid.org/0000-0002-2571-2405)
- J. Silvio Gutkind (ORCID: https://orcid.org/0000-0002-5150-4482)
- Farhoud Faraji (ORCID: https://orcid.org/0000-0001-5078-813X)
- Alfredo Molinolo (ORCID: https://orcid.org/0000-0001-8412-2889)
- Tomohiko Ishikawa (ORCID: https://orcid.org/0000-0003-3115-0047)
- Scott M. Lippman (ORCID: https://orcid.org/0000-0002-1643-4124)
- Xingyu Wu (ORCID: https://orcid.org/0000-0001-9289-7115)
- Prashant Mali (ORCID: https://orcid.org/0000-0002-3383-1287)
- Kai-Xi Fan (ORCID: https://orcid.org/0009-0001-4801-6090)
- Tracy Guo (ORCID: https://orcid.org/0009-0001-1438-985X)
Institutions
- La Jolla Institute for Immunology (US)
- University of San Diego (US)
- National Foundation for Cancer Research (US)
- UC San Diego Health System (US)
- University of California System (US)
- University of California San Diego (US)
- La Jolla Bioengineering Institute (US)
- La Jolla Institute For Molecular Medicine (US)
Publication Details
- Journal
- Cancer Prevention Research
- Published
- 2025-12-19
- DOI
- https://doi.org/10.1158/1940-6207.capr-25-0264
- Primary Topic
- Metabolism, Diabetes, and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00