MCV and Merkel cell carcinoma: a molecular success story.

Merkel cell polyomavirus (MCV), discovered in 2008, is clonally integrated in ~80% Merkel cell carcinoma (MCC). MCV is a common skin flora and initiates cancer in susceptible hosts only after it acquires a precise set of mutations that render it replication incompetent. Both MCV large and small T proteins promote cancer cell survival and proliferation. Large T targets pocket proteins regulating cell cycle transit while small T activates cap-dependent translation critical for cancer cell growth. These findings already have led to new diagnostics and clinical trials to target MCV-induced survivin and to promote antitumor immunity. In four years, the cause, diagnosis and therapy for an intractable cancer has been changed due to the molecular discovery of MCV.