Present role and future potential of type I interferons in adjuvant therapy of high-risk operable melanoma

Few molecular therapeutic approaches have been so rigorously investigated in relation to the pathophysiology and outcome of human diseases as type I interferons. Historically, IFNs were discovered after the phenomenon of 'interference' was first described by Isaacs and Lindenmann in 1957, and for years IFNs (IFNalpha) were considered as potential "antiviral penicillins" until the broader spectrum of effects upon normal cell physiology, the natural and adaptive immune systems, and tumor growth and proliferation were described. Interferon beta (IFNbeta) was the second human gene after insulin to be cloned, and it codes for the first cytokine used to treat human malignancies. Despite the progress in understanding and treating cancer over the last 25 years, IFN alpha (IFNalpha) remains the most commonly used biologically active cytokine in the treatment of solid tumors, and for some like melanoma, the only successful agent. In this review we discuss the role of type I interferons in the pathophysiology and treatment of melanoma, with emphasis on the 22 years of work conducted at the University of Pittsburgh. We discuss potential mechanisms that partially explain the clinical benefit, and set the groundwork for building upon, the design of more effective treatments for this disease.