Advances in Biology and Therapy of Multiple Myeloma

1. Front Matter

   Pages i-x

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2. Myeloma Molecular Pathways and Cell Signaling

   1. Front Matter

      Pages 1-1

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   2. Genomic Strategies Determining Progression from MGUS to Multiple Myeloma

      • Esteban Braggio, Rafael Fonseca

      Pages 3-24

   3. Prognostic Implication of Genetic Changes (Cytogenetics, and FISH, Gains and Losses of DNA by SNP Array and aCGH) in Risk Stratification in Myeloma

      • Jill Corre, Hervé Avet-Loiseau

      Pages 25-39

   4. Advances in Multiple Myeloma Gene-Expression Profiling

      • Saad Usmani, B. Barlogie, J. D. Shaughnessy Jr.

      Pages 41-63

   5. Growth Factors in Multiple Myeloma

      • Jérôme Moreaux, Caroline Bret, Karène Mahtouk, Anne-Catherine Sprynski, Dirk Hose, Bernard Klein

      Pages 65-84

   6. Role of Wnt Signaling Pathways in Multiple Myeloma Pathogenesis

      • Mariateresa Fulciniti, Daniel R. Carrasco

      Pages 85-95

   7. The mTOR Pathway in Multiple Myeloma

      • Joseph Gera, Alan Lichtenstein

      Pages 97-116

   8. Jak/STAT Signaling in the Pathogenesis and Treatment of Multiple Myeloma

      • Erik A. Nelson, Sarah R. Walker, David A. Frank

      Pages 117-138

3. Myeloma Microenvironment

   1. Front Matter

      Pages 139-139

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   2. The Bone Marrow Microenvironment: Novel Targets to Circumvent Minimal Residual Disease and Drug Resistance in Multiple Myeloma

      • Kenneth H. Shain, William S. Dalton

      Pages 141-168

   3. Osteoclasts: Potential Target for Blocking Microenvironmental Support of Myeloma

      • Deborah L. Galson, Sonia D’Souza, G. David Roodman

      Pages 169-185

   4. Targeting the BAFF/APRIL Cytokine Network in Multiple Myeloma

      • Stephen A. Mihalcik, Diane F. Jelinek

      Pages 187-202

   5. Role of Osteoblast in Myeloma Pathology

      • Sonia Vallet, Noopur Raje

      Pages 203-214

   6. Migration and Homing in Multiple Myeloma

      • Giada Bianchi, Irene M. Ghobrial

      Pages 215-239

   7. Genes and Proteins of Myeloma Endothelial Cells to Search Specific Targets of the Tumor Vasculature

      • Domenico Ribatti, Angelo Vacca

      Pages 241-254

   8. Epigenetic Regulation of Myeloma Within Its Bone Marrow Microenvironment

      • Elke De Bruyne, Ken Maes, Sarah Deleu, Els Van Valckenborgh, Eline Menu, Isabelle Vande Broek et al.

      Pages 255-282

   9. Targeting Multiple Myeloma Tumor Angiogenesis: Focus on VEGF

      • Klaus Podar, Kenneth C. Anderson

      Pages 283-299

   10. Novel In Vivo Models in Myeloma

       • Eric Sanchez, Haiming Chen, James R. Berenson

       Pages 301-312

4. Back Matter

   Pages 313-319

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Despite the advances in conventional, novel agent and high dose chemotherapy multiple myeloma (MM) remains incurable. In order to overcome resistance to current therapies and improve patient outcome, novel biologically-based treatment approaches are being developed. Current translational research in MM focusing on the development of molecularly-based combination therapies has great promise to achieve high frequency and durable responses in the majority of patients. Two major advances are making this goal possible. First, recent advances in genomics and proteomics in MM have allowed for increased understanding of disease pathogenesis, identified novel therapeutic targets, allowed for molecular classification, and provided the scientific rationale for combining targeted therapies to increase tumor cell cytotoxicity and abrogate drug resistance. Second, there is now an increased understanding of how adhesion of MM cells in bone marrow (BM) further impacts gene expression in MM cells, as well as in BM stromal cells (BMSCs). As a result of these advances in oncogenomics on the one hand and increased understanding of the role of the BM in the pathogenesis of MM on the other, a new treatment paradigm targeting the tumor cell and its BM microenvironment to overcome drug resistance and improve patient outcome has now been developed. Thalidomide, lenalidomide, and Bortezomib are three agents which target the tumor cell in its microenvironment in both laboratory and animal models and which have rapidly translated from the bench to the bedside. Ongoing efforts are using oncogenomics and cell signaling studies to identify next generation of therapies in MM on the one hand, and to inform the design of combination trials on the other. This new paradigm for overcoming drug resistance and improving patient outcome in MM has great promise not only to change the natural history of MM, but also to serve as a model for targeted therapeutics directed to improve outcome of patients with MM.

• Kahler's disease
• MGUS
• cancer
• hematological malignancy
• plasma cell myeloma
• plasma cells

• Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA

  Nikhil C. Munshi

• Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Boston, USA

  Kenneth C. Anderson

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