Redefining the role of interferon in the treatment of malignant diseases

Interferon (IFN) is a cytokine with a long history of use as immunotherapy in the treatment of various solid tumours and haematological malignancies. The initial use of IFN in cancer therapy was based on its antiproliferative and immunomodulatory effects, and it has been shown more recently to have cytotoxic and anti-angiogenic properties. These features make it a rational anticancer therapy; however, advances in our understanding of the molecular mechanisms involved in cancer development and growth and the availability of effective, alternative therapies have led to IFN therapy being superseded in many cancers. IFN is still commonly used in renal cell carcinoma (RCC), melanoma and myeloproliferative disorders, in which its optimal dose and treatment duration remain to be established despite extensive clinical experience. Preclinical. studies of the mechanism of action of IFN suggest that different antitumour effects are relevant at different doses, providing a rationale to explore the use of different dose regimens of IFN, particularly when combined with other therapies. In particular, the advent of novel anti-angiogenic therapies in RCC means that the role of IFN needs to be re-examined with a focus on how best to maximise efficacy and minimise toxicity when used with these agents. This review will focus on the therapeutic use of IFN in these disorders, provide an overview of available data and consider what the data suggest regarding the potential optimal use of IFN in the future. (C) 2009 Elsevier Ltd. All rights reserved.