期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 32, 期 6, 页码 829-841出版社
WILEY
DOI: 10.1111/pcmr.12807
关键词
binimetinib; MK-2206 2HCl; mouse model; PD-0325901; S6
资金
- Ligue Contre le Cancer
- Fondation ARC
- Institut Carnot
- INCa
- ITMO Cancer
- ANR Labex CelTisPhyBio [ANR-11-LABX-0038, ANR-10-IDEX-0001-02]
- MENRT
- Department of Defense [W81XWH-18-1-0224]
- Sheldon G. Adelson Medical Research Foundation
- NCI Cancer Center [CA16672]
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 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 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.
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