A new ERK1/2 inhibitor showed clinical activity in patients with NRAS and BRAF-mutant solid tumors.

2018-03-31

MAPK signaling pathway is an important signaling pathway in cancer cells. Aberrations of the RAS, RAF and MEK are known to activate MAPK signaling. The activation of the MAPK signaling pathway will stimulate proliferation, differentiation, and cell survival. Several treatment strategies that inhibits BRAF and MEK have been developed. Another approach to inhibit MAPK signaling is targeting the downstream molecular ERK1/2. In a multicenter phase I trial (NCT01781429), patients with NRAS, BRAF or MEK-mutated advanced solid tumor were treated with ulixertinib, an ERK1/2 inhibitor, to identify its safeness and clinical activity. The trial identified the maximum tolerated dose and the recommended phase II dose. This preliminary analysis of ulixertinib showed durable objective responses not only in patients with NRAS and BRAF V600 mutations, but also in those with BRAF non-V600 mutations, including L485W and G469A mutations. These results demonstrated that ulixertinib was well tolerated and had the potential in treating cancer patients with NRAS and BRAF mutations.

Source: Sullivan RJ, Infante JR, Janku F, et al. Cancer Discov. 2018;8(2):184-195.

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