C57BL/6 congenic mouse NRASQ61K melanoma cell lines are highly sensitive to the combination of Mek and Akt inhibitors in vitro and in vivo
Abstract
RAS is frequently mutated in various tumors and known to be difficult to target. NRASQ61K/R are the second most frequent mutations found in human skin melanoma after BRAFV600E. Aside from surgery, various approaches, including targeted therapies, immunotherapies, and combination therapies, are used to treat patients carrying NRAS mutations, but they are inefficient. Here, we established mouse NRASQ61K melanoma cell lines and genetically derived isografts (GDIs) from Tyr::NRASQ61K mouse melanoma that can be used in vitro and in vivo in an immune‐competent environment (C57BL/6) to test and discover novel therapies. We characterized these cell lines at the cellular, molecular, and oncogenic levels and show that NRASQ61K melanoma is highly sensitive to the combination of Mek and Akt inhibitors. This preclinical model shows much potential for the screening of novel therapeutic strategies for patients harboring NRAS mutations that have limited therapeutic options and resulted in poor prognoses.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 15, 2019
- Source ID
- 10.1111/pcmr.12807
Entities
People
- Andrew E Aplin
- Christophe Alberti
- Jeremy Raymond
- Lionel Larue
- Mai Q. Nguyen
- Marie Pouteaux
- Stuart J. Gallagher
- Valérie Petit
- Véronique Delmas
Organizations
- Fondation ARC pour la recherche sur le cancer
- Institut National du Cancer
- National League Against Cancer
- PSL Research University
- Sidney Kimmel Comprehensive Cancer Center
- Thomas Jefferson University
- United States Department of Defense