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Association details:
Biomarker:NRAS mutation
Cancer:Melanoma
Drug:XL888 (HSP90 inhibitor)
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: D – Preclinical
New
Title:

Inhibition of Wee1, AKT, and CDK4 Underlies the Efficacy of the HSP90 Inhibitor XL888 in an In Vivo Model of NRAS-Mutant Melanoma

Excerpt:
Treatment of a panel of 9 NRAS-mutant human melanoma cell lines with XL888 (Fig. 1) was associated with concentration-dependent decreases in cell growth...The growth inhibitory effects of XL888 were associated with the induction of a G2–M phase cell-cycle arrest (Fig. 2B) and robust levels of apoptosis by 72 hours (Fig. 2C). No colony formation was observed for any of the 4 cell lines following chronic XL888 (Fig. 2D), with complete eradication of all M318 cells being observed at XL888 concentrations as low as 10 nmol/L...
DOI:
10.1158/1535-7163.MCT-12-1003