Inflammatory mediators as therapeutic targets for inflammatory breast cancer

Fredika M. Robertson*, Khoi Chu, Rita Circo, Julia Wulfkuhle, Lance Liotta, Annie Z. Luo, Kimberly M. Boley, Erik M. Freiter, Hui Liu, Pijus K. Mandal, John S. Mc Murray, Massimo Cristofanilli, Emanuel F. Petricoin

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The molecular signature of inflammatory breast cancer (IBC) includes activation of target genes of the nuclear factor-kappa B (NF-kB) transcription factor. These NF-kB target genes are differentially activated in IBC tumors and primarily produce pro-inflammatory mediators such as the chemokine interleukin-8 (IL-8), the lipid mediator prostaglandin E2, the chemokine receptor CXCR4 and its ligand partner CXCL12, and the axis defined by IL-6/Janus kinases and signal tranducer and activator of transcription 3 (STAT3). While these genes are known to regulate innate immune responses, they also are critically important to survival of tumor cells and to metastatic progression. Ongoing research is defining the roles of these inflammatory mediators and associated signaling pathways in breast cancer, in general, and in IBC. Some of these studies have evaluated pharmacological and biological agents that effectively target these pro-inflammatory mediators and have led to development of new therapeutics that may effectively abrogate IBC growth and metastasis. In summary, this chapter reviews the inflammatory mediators that have been identified as part of the molecular fingerprint of IBC and describes new evidence for the potential for inhibitors of these mediators to target specific populations of cells within IBC tumors that contribute to tumor initiation and metastatic progression.

Original languageEnglish (US)
Title of host publicationInflammatory Breast Cancer
Subtitle of host publicationAn Update
PublisherSpringer Netherlands
Pages185-205
Number of pages21
ISBN (Electronic)9789400739079
ISBN (Print)9789400739062
DOIs
StatePublished - Jan 1 2012

Keywords

  • CXCR4
  • Cancer stem cells
  • Cox-2
  • Inflammatory breast cancer
  • Interleukin-6
  • Interleukin-8
  • JAK
  • Metastasis
  • NF-kB
  • STAT3

ASJC Scopus subject areas

  • Medicine(all)

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