Selumetinib

Selumetinib, activating mutations in the BRAF V600E, are associated with poorer outcomes in patients with papillary thyroid cancer. MAPK kinase (MEK), immediately downstream of BRAF, is a promising target for MAPK/ERK pathway inhibition. In addition to thyroid cancer, BRAF-activating mutations are prevalent in melanoma (–59%), colorectal cancer (5–22%), serous ovarian cancer (–30%), and several other tumor types. Four lines bearing V600E BRAF mutations were all sensitive to selumetinib, with GI50 values ranging from 14 to 50 nM. A positive control BRAF mutant melanoma line, SKMel28, exhibited a similar GI50 of 23 nM. A Phase II clinical trial about selumetinib in cancers with BRAF mutations is ongoing.