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Inflammatory Mediators as Therapeutic Targets for Inflammatory Breast Cancer

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Inflammatory Breast Cancer: An Update

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Abstract

The molecular signature of inflammatory breast cancer (IBC) includes activation of target genes of the nuclear factor-kappa B (NF-κB) transcription factor. These NF-κB 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.

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Abbreviations

bFGF:

basic fibroblast growth factor

Cox-2:

cyclooxygenase-2

CXCL:

chemokine (C-X-C motif) ligand

CXCR:

C-X-C chemokine receptor

EGFR:

epidermal growth factor receptor

EP:

prostanoid receptor

ER:

estrogen receptor

GROα:

growth-related oncogene alpha

IBC:

inflammatory breast cancer

IL:

interleukin

JAK:

Janus kinase

MAPK:

mitogen-activated protein kinase

NF-κB:

nuclear factor kappa B

PGE2 :

prostaglandin E2

PI3K:

phosphatidylinositol 3 kinase

RANKL:

receptor activator of nuclear factor kappa B

sIL-6R:

soluble interleukin-6 receptor

STAT3:

signal transducers and activators of transcription 3

VEGF:

vascular endothelial growth factor

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Acknowledgments

Supported by the American Airlines-Komen For the Cure Foundation Promise Grant KGO81287 (FMR, MC) and The State of Texas Fund for Rare and Aggressive Breast Tumors (FMR). The authors appreciate the generous support of Dr. Vikas Chandhoke and the College of Life Sciences at George Mason University. This work was partially supported by the Italian Istituto Superiore di Sanità within the framework Italy/USA cooperation agreement between the U.S. Department of Health and Human Services, George Mason University, and the Italian Ministry of Public Health.

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Authors and Affiliations

  1. The Department of Experimental Therapeutics and The Center for Targeted Therapy, Unit 1950, The University of Texas MD Anderson Cancer Center, 301429, South Campus Research Building 4, 3.1009, Houston, TX, 77230-1429, USA

    Fredika M. Robertson Ph.D., Khoi Chu Ph.D., Annie Z. Luo M.D., Kimberly M. Boley, Erik M. Freiter B.S., Hui Liu Ph.D., Pijus K. Mandal Ph.D. & John S. McMurray Ph.D.

  2. The Morgan Welch Inflammatory Breast Cancer Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Fredika M. Robertson Ph.D.

  3. Istituto Superiore di Sanità, Rome, Italy

    Rita Circo Ph.D.

  4. The Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA

    Rita Circo Ph.D., Julia Wulfkuhle Ph.D., Lance Liotta M.D., Ph.D. & Emanuel F. Petricoin Ph.D.

  5. Department of Medical Oncology, Fox Chase Cancer Center, Cottman Avenue, Room C315 333, Philadelphia, PA, USA

    Massimo Cristofanilli

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  1. Fredika M. Robertson Ph.D.
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  13. Emanuel F. Petricoin Ph.D.
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Correspondence to Fredika M. Robertson Ph.D. .

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Editors and Affiliations

  1. MD Anderson Cancer Center, Dept. Breast Medical Oncology, University of Texas, Holcombe Blvd. 1515, Houston, 77030-4095, Texas, USA

    Naoto T. Ueno

  2. Fox Chase Cancer Center, Cottman Avenue; Room C315 333, Philadelphia, 19111, Pennsylvania, USA

    Massimo Cristofanilli

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Robertson, F.M. et al. (2012). Inflammatory Mediators as Therapeutic Targets for Inflammatory Breast Cancer. In: Ueno, N., Cristofanilli, M. (eds) Inflammatory Breast Cancer: An Update. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3907-9_16

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