The Melanoma Letter Spring 2014, Vol. 32, No. 1

In the past few years, we have seen unprecedented gains in the treatment of metastatic melanoma. This disease in its advanced stages has always had a dire prognosis, with patients on average surviving a matter of months. But we have entered an era when cures are increasingly occurring, with some patients living 5-10 years and counting. "Targeted therapy," inhibiting specific defective genes that switch on melanoma and certain brakes on the immune system that stop t-cells from attacking, has been the springboard for this revolution. It now often replaces chemotherapy’s scattershot attack on both diseased and healthy cells or relegates it to a complementary role. In our lead story, Drs. Momtaz, Lacouture, and Chapman explore in detail just how far we’ve come in this targeted revolution, and how much further we have to go.

Additionally, researchers are now seeking ways to defeat melanoma cells’ eventual resistance to treatment that in most cases ultimately derails therapies, leading to recurrences. To date, patients taking vemurafenib or dabrafenib, the two recently FDA-approved drugs that inhibit the defective BRAF gene found in half of all melanomas, usually end up facing this resistance. In our fascinating second story, Dr. Martin McMahon and Marian Deuker discuss their research into intermittent dosing with BRAF inhibitors as one means of creating such a homeostasis.