Interferon-lambda as a potential therapeutic agent in cancer treatment - PubMed (original) (raw)

Review

Interferon-lambda as a potential therapeutic agent in cancer treatment

Håkan C Steen et al. J Interferon Cytokine Res. 2010 Aug.

Abstract

The discovery that type I interferon (IFN-alpha/beta) inhibited tumor cell growth was welcomed initially with great excitement as it rapidly became a U.S. Food and Drug Administration-approved drug to treat several forms of cancer. In time, this enthusiasm diminished as severe toxicity associated with IFN-alpha administration, resistance to the therapy, or less than optimal responses became evident in cancer patients, thus restricting its clinical use and reducing its potential as an anticancer drug. The recent discovery of a third type of IFN [IFN-lambda/interleukin (IL)-29/IL-28], which shares the same biological properties of type I IFNs, opens the door for evaluating the therapeutic potential of IFN-lambda as it uses a distinct receptor complex whose expression, unlike type I IFN receptors, is restricted to cells of specific lineage. It is unclear whether the mechanism by which type III IFNs restrict tumor cell proliferation is different or the same from the one utilized by type I IFN. Nevertheless, accumulating evidence as described in this review suggests that, in contrast to IFN-alpha therapy, IFN-lambda therapy could be less toxic and suitable for certain types of malignancies as not all cells are responsive to this cytokine.

PubMed Disclaimer

Conflict of interest statement

No potential conflicts of interest were disclosed.

Figures

FIG. 1.

FIG. 1.

Metastatic but not primary melanoma tumor cells respond to IFN-λ. Paired primary and metastatic melanoma tumor cell lines from 3 patients were stimulated with IFN-α, IFN-λ, or IFN-γ for 20 min. IFN-λ responsiveness was measured by immunoblot analysis of phosphotyrosine-701 STAT1. IFN, interferon.

Similar articles

Cited by

References

    1. Abbas T. Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev. 2009;9:400–414. . - PMC - PubMed
    1. Ank N. West H. Bartholdy C. Eriksson K. Thomsen AR. Paludan SR. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol. 2006;80:4501–4509. . - PMC - PubMed
    1. Brand S. Beigel F. Olszak T. Zitzmann K. Eichhorst ST. Otte JM. Diebold J. Diepolder H. Adler B. Auernhammer CJ. Goke B. Dambacher J. IL-28A and IL-29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL-28A expression. Am J Physiol. 2005;289:G960–G968. . - PubMed
    1. Chawla-Sarkar M. Lindner DJ. Liu YF. Williams BR. Sen GC. Silverman RH. Borden EC. Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis. 2003;8:237–249. . - PubMed
    1. Dellgren C. Gad HH. Hamming OJ. Melchjorsen J. Hartmann R. Human interferon-lambda3 is a potent member of the type III interferon family. Genes Immun. 2009;10:125–131. . - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources