Dr. Richard D. Carvajal on the Investigation of Selumetinib

Richard D. Carvajal, MD, medical oncologist, Memorial Sloan-Kettering Cancer Center, discusses the background of the investigation of selumetinib for advanced uveal melanoma.

In 2008, Carvajal says, two independent laboratories identified frequent mutations in gnaq and Gna11 in uveal melanoma. These genes encode for G alpha subunits, which function to mediate signaling from cell surface receptors to downstream signaling pathways. With these mutations, Carvajal says, growth pathways, including the MAP kinase pathway, are activated. Researchers hypothesized that the inhibition of that MAP kinase pathway, perhaps at the level of MEK, could lead to clinical efficacy for selumetinib.

Researchers conducted a series of preclinical experiments to demonstrate that MEK inhibition works. Preclinical data showed that patients with uveal melanoma treated on prior studies with selumetinib experienced benefit, which led to the development of another trial to more definitively assess the benefits of MEK inhibition in this disease.