C57BL/6 congenic mouse NRASQ61K melanoma cell lines are highly sensitive to the combination of Mek and Akt inhibitors in vitro and in vivo. (15th July 2019)

• Record Type: Journal Article
• Authors: Petit, Valérie; Raymond, Jeremy; Alberti, Christophe; Pouteaux, Marie; Gallagher, Stuart J.; Nguyen, Mai Q.; Aplin, Andrew E.; Delmas, Véronique; Larue, Lionel
• Is Part Of: Pigment cell & melanoma research. Volume 32:Number 6(2019)
• Page Start: 829
• Page End: 841
• Publication Date: 2019-07-15
• Subjects: binimetinib -- MK‐2206 2HCl -- mouse model -- PD‐0325901 -- S6; Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12807
• Languages: English
• ISSNs: 1755-1471

Abstract

Abstract: RAS is frequently mutated in various tumors and known to be difficult to target. NRAS Q61K/R are the second most frequent mutations found in human skin melanoma after BRAF V600E . 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 NRAS Q61K melanoma cell lines and genetically derived isografts (GDIs) from Tyr::NRAS Q61K 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 NRAS Q61K 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.