Interferons: mechanisms of action and clinical applications

Curr Opin Oncol. 2003 Nov;15(6):431-9. doi: 10.1097/00001622-200311000-00005.

Abstract

Purpose of review: Interferons are pleiotropic cytokines that exhibit important biologic activities, including antiviral, antitumor, and immunomodulatory effects. These cytokines have found important applications in clinical medicine, including the treatment of certain malignancies. The purpose of this review is to provide an update on basic and clinical research in the interferon field.

Recent findings: Significant advances have recently occurred in the field of type I interferon signal transduction. It is well known that the interferons transduce signals via activation of multiple signaling cascades, involving Jak kinases, signal transducer and activator of transcription proteins, Map kinases, and IRS and Crk proteins. Recent evidence indicates that the p38 Map kinase pathway plays an important role in type I interferon signaling in malignant cells and that its function is required for type I interferon-dependent gene transcription and generation of the antiproliferative of type I interferons. In clinical oncology, interferon-alpha remains an active and useful agent in the treatment of several malignant disorders, and efforts are underway to improve its efficacy by using different schedules and combinations with other agents.

Summary: This review summarizes the mechanisms of signal transduction of interferons and the emerging new concepts in this area. An update on the clinical applications of interferons in oncology is also provided, and potential translational applications, reflecting recent advances in the field, are discussed.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport / drug effects
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Apoptosis / drug effects
  • Humans
  • Interferons / metabolism*
  • Interferons / therapeutic use*
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Proto-Oncogene Proteins c-crk
  • Receptor, Insulin / drug effects
  • Receptor, Insulin / metabolism
  • Receptors, Interferon / metabolism
  • Receptors, Interferon / therapeutic use
  • Signal Transduction / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • CRK protein, human
  • Proto-Oncogene Proteins c-crk
  • Receptors, Interferon
  • Interferons
  • Receptor, Insulin
  • Mitogen-Activated Protein Kinases