The anticancer face of interferon alpha (IFN-alpha): from biology to clinical results, with a focus on melanoma.

Alpha interferons (IFN) are type I IFNs that have pleiotropic effects on cell functions. A wealth of evidence exists that these cytokines exhibit a variety of biological effects different from those on viral replication, including antitumor activity. IFNs-alpha represent the cytokines exhibiting the longest record of use in clinical oncology for the treatment of over a dozen of cancer types, including some hematological malignancies and solid tumors. Although targeted anticancer agents have recently replaced IFN-alpha in the treatment of certain hematological (e.g. chronic myeloid leukemia) and solid (e.g. renal cell carcinoma) malignancies, this cytokine is still used for the treatment of patients with specific tumor types, such as cutaneous melanoma. Despite the intense work in preclinical tumor models and considerable experience in the clinical use of IFN-alpha, the mechanisms of action underlying tumor response is still a matter of open debate. In this review we describe the evidence supporting the main mechanisms underlying IFN-alpha anticancer effects using both preclinical and clinical findings; moreover, we focus on the results of IFN-alpha for the treatment of patients with high-risk cutaneous melanoma, one of the malignancies most resistant to conventional chemotherapy.