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Cytokines and Signal Transduction in Multiple Myeloma

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Neoplastic Diseases of the Blood

Abstract

Multiple Myeloma (MM) is diagnosed in 15,000 new individuals each year. The median survival has been prolonged from 3–4 to 7 years, especially in patients less than age 50 [1–3]. Despite recent advances including biological agents bortezomib, thalidomide, and lenalidomide, MM remains incurable due to the development of drug resistance, which manifests as relapsed/refractory disease [4, 5]. The molecular and cellular mechanisms whereby MM cells evade drug-induced cytotoxicity and acquire drug-resistant phenotypes include interaction of MM cells with cellular components within the bone marrow (BM) microenvironment [5]. MM cells predominantly reside in the BM and adhere both to the extracellular matrix (ECM) proteins and BM stromal cells (BMSCs) due to binding via adhesion molecules. This interaction between tumor cells and BMSCs not only localizes tumor cells in the BM, but also confers protection against apoptosis and triggers secretion of cytokines mediating autocrine [6, 7] and paracrine [8–11] growth of MM cells. Examples of cytokines include IL-6, IL-21, vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), B-cell stimulating factor 3 (BSF-3), tumor necrosis factor-α (TNF-α), stromal cell-derived factor 1α (SDF-1α), and fibroblast growth factor (FGF). Importantly, new and effective therapeutic strategies have been derived based upon targeting these cytokines and their signaling cascades both in MM cells and in the BM microenvironment. This chapter reviews the role of various cytokines in the biology of MM, as well as novel therapies that overcome cytokine-mediated growth, survival, migration, and drug-resistance.

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Acknowledgments

Supported by NIH Grants SPORE-P50100707, PO1-CA078378, and RO1CA050947; and MRF funds.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street M561, Boston, MA, 02115, USA

    Dharminder Chauhan Ph.D. & Kenneth C. Anderson M.D.

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  1. Dharminder Chauhan Ph.D.
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  2. Kenneth C. Anderson M.D.
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Correspondence to Dharminder Chauhan Ph.D. .

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  1. Beth Israel Hospital, Cancer Center, St. Lukes-Roosevelt Hospital Center, 10th Avenue 1000, New York, 10019, New York, USA

    Peter H. Wiernik

  2. , Department of Hematology, Imperial College of London, Du Cane Road 150, London, W12 0NN, United Kingdom

    John M. Goldman

  3. Continuum Cancer Centers, Department of Medicine, St. Luke's-Roosevelt Hospital Center, 10th Avenue 1000, New York, 10019, New York, USA

    Janice P. Dutcher

  4. , Division of Hematology, Mayo Clinic, First Street SW. 200, Rochester, 55905, Minnesota, USA

    Robert A. Kyle

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Chauhan, D., Anderson, K.C. (2013). Cytokines and Signal Transduction in Multiple Myeloma. In: Wiernik, P., Goldman, J., Dutcher, J., Kyle, R. (eds) Neoplastic Diseases of the Blood. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3764-2_27

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