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Cytokines in the Genesis and Treatment of Cancer pp 181–197Cite as

Cytokines in Multiple Myeloma

Therapeutic Implications

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Multiple myeloma (MM) is a clonal plasma cell neoplasm which remains incurable despite conventional therapy; and new treatment strategies are therefore urgently required (1,2). MM cells predominantly localize in bone marrow (BM), and their interaction with BM stromal cells (BMSCs) stimulates transcription and secretion of cytokines from BMSCs. Cytokines in turn not only promote the growth and survival of MM cells, but also reduce efficacy of conventional drugs (2). For example, adherence of MM cells to BMSCs triggers interleukin-6 (IL-6) and insulin-like growth factor-I (IGF-I), and vascular endothelial growth factor (VEGF) production from BMSCs, which induces MM cell growth and protect against dexamethasone (Dex)-induced MM apoptosis (3–8). High serum levels of IL-6 and IGF-I in MM patients (9,10) also correlate with clinical drug-resistance in MM. Cytokines trigger three signaling cascades in MM cells: mitogen-activated extracellular kinase 2(MEK)/extracellular signal-regulated kinase (ERK); phosphatidylinositol-3 kinase (PI3-kinase)/AKT; and Janus kinases (JAK)-signal transducer and activator of transcription (STAT) pathways. Novel treatment strategies based on targeting these signaling pathways are now being designed to block cytokine-mediated growth/survival and drug-resistance. In this chapter, we review the role of various cytokines in the biology of MM, as well as novel therapies that overcome cytokine-mediated growth, survival, migration and chemoresistance.

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Authors and Affiliations

  1. The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA

    Dharminder Chauhan JD, PHD, Teru Hideshima PHD & Kenneth C. Anderson MD

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  1. Dharminder Chauhan JD, PHD
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  2. Teru Hideshima PHD
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  3. Kenneth C. Anderson MD
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Editors and Affiliations

  1. The Ohio State University Comprehensive Cancer Center, Columbus, OH

    Michael A. Caligiuri MD

  2. University of Pittsburgh Cancer Center, Pittsburgh, PA

    Michael T. Lotze MD (Director) (Director)

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Chauhan, D., Hideshima, T., Anderson, K.C. (2007). Cytokines in Multiple Myeloma. In: Caligiuri, M.A., Lotze, M.T. (eds) Cytokines in the Genesis and Treatment of Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-455-1_10

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  • DOI: https://doi.org/10.1007/978-1-59745-455-1_10

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