RAS is frequently mutated in various tumors and known to be difficult to target. In human skin cutaneous melanoma, mutations of NRAS are the second most frequent mutations of driver genes after BRAF mutations. Aside from surgery, different treatment as targeted therapies and immunotherapies are used to treat/cure patient melanoma harboring NRAS mutations, but they lack of efficiency. Here, we established mouse NRASQ61K and mouse derived isografts from Tyr::NRASQ61K mouse melanoma that can be used both in vitro and in vivo in an immune-competent environment (C57BL/6J). These models will be useful to better understand NRAS melanoma cellular, molecular and oncogenic process and to discover novel therapies. These cell lines were characterized at both cellular, molecular and oncogenic level showing that NRASQ61K 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 patient harboring NRAS mutation.

C57BL/6 CONGENIC MOUSE NRASQ61K MELANOMA CELL LINES ARE HIGHLY SENSITIVE TO THE COMBINATION OF MEK AND AKT INHIBITORS IN VITRO AND IN VIVO