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Towards a new age in the treatment of multiple myeloma

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Abstract

Multiple myeloma (MM) is an incurable disease characterized by the proliferation of end-stage B lymphocytes (plasma cells, PCs). As a consequence of myeloma growth in the bone marrow, a number of signaling pathways are activated that trigger malignant PC proliferation, escape from apoptosis, migration, and invasion. Thanks to new insights into the molecular pathogenesis of MM, novel approaches aimed at targeting these abnormally activated cascades have recently been developed and others are under study. These strategies include the inhibition of membrane receptor tyrosine kinases, inhibition of the proteasome/aggresome machinery, inhibition of histone deacetylases, inhibition of farnesyltransferases, targeting of molecular chaperones, and others. We will herein review and discuss these novel biological approaches with particular emphasis on those based on biochemical pathways which drive cell signaling. By providing the rationale for innovative therapeutic strategies, the above mechanisms represent targets for new compounds being tested in the management of this disease.

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Acknowledgements

We are grateful to all the members of the Unit of Hematological Malignancies at VIMM and of the Hematology-Immunology Section at Padua University Hospital for support and suggestions. We thank M. E. Donach for reading the manuscript. Work in G.S. Lab is supported by grants from the International Myeloma Foundation (to F.A.P.), from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and Istituto Oncologico Veneto (IOV).

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  1. Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy

    Francesco A. Piazza, Carmela Gurrieri, Livio Trentin & Gianpietro Semenzato

  2. Venetian Institute of Molecular Medicine, Haematological Malignancies Unit, Padua University School of Medicine, Padova, Italy

    Francesco A. Piazza, Carmela Gurrieri, Livio Trentin & Gianpietro Semenzato

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  1. Francesco A. Piazza
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Correspondence to Gianpietro Semenzato.

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Piazza, F.A., Gurrieri, C., Trentin, L. et al. Towards a new age in the treatment of multiple myeloma. Ann Hematol 86, 159–172 (2007). https://doi.org/10.1007/s00277-006-0239-5

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