ABSTRACT
Interferons (IFNs) were first described as potent antiviral agents in 1957 by Isaacs and Lindenmann.1 They were later shown to have pleiotropic functions not only in antiviral control but also in control of cell proliferation and in modulation of the immune system. The discovery that IFNs inhibit the growth of normal and malignant hematopoietic cells in vitro and in vivo led to pivotal phase I clinical studies using recombinant IFN- in 1982.2 IFNs were the first cytokines made available for clinical trials in cancer patients. Since then, the antitumor activity of IFN- has been well documented in a variety of solid and hematologic malignancies. Today, recombinant IFN- is approved worldwide in over 40 countries for the therapy of a variety of malignant and viral diseases, including condyloma acuminata, hepatitis B and C, non-Hodgkin’s lymphoma, and chronic myeloid leukemia (CML).3
However, the precise mechanism by which IFN- works in the therapy of malignancies is still unknown. The same holds for our knowledge of the molecular mechanism of clinical resistance to IFN-. This chapter will highlighten signal transduction of IFN- and some of the direct and indirect effects that are
