Publication date: Apr 30, 2019
Melanoma is one of the most common cutaneous cancers worldwide. Activating mutations in RAS oncogenes are found in a third of all human cancers and NRAS mutations are found in 15%-20% of melanomas. Acquisition of a functional mutation in NRAS results in activation of the Ras / Raf / MEK / ERK signaling pathway leading to unconstrained cell growth and cell transformation. NRAS mutation status was identified as an independent poor prognostic factor in stage IV melanoma. No drug was approved to treat melanoma patients with NRAS mutation or amplification until now. FCN-159, an oral and potent MEK1/2 inhibitor, has more than 10 folds higher selectivity against activated MEK1 and MEK2 compared with trametinib, and has demonstrated significant antitumor growth inhibition in two patient-derived xenograft (PDX) models with NRAS mutation.This is the first in human study to evaluate the safety and anti-tumor activity in patients.
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