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.
Volume 1 Ch. 1 Genomic strategies determining progressions from MGUS to Multiple Myeloma Ch. 2 Prognostic implication of Genetic changes (Cytogenetics, and FISH, gains and losses of DNA by SNP array and aCGH) in risk stratification in myeloma Ch. 3 Advances in MM gene expression profiling Ch. 4 Growth factors in MM Ch. 5 Role of Wnt signaling pathways in multiple myeloma pathogenesis Ch. 6 mTOR pathway in multiple myeloma Ch. 7 Jak/STAT signaling in the pathogenesis and treatment of multiple myeloma Ch. 8 Role of extracellular matrix in myeloma biology Ch. 9 Osteoclasts: Potential target for blocking microenvironmental support of myeloma Ch. 10 Targeting the BAFF/APRIL cytokine network in multiple myeloma Ch. 11 Role of Osteoblast in myeloma pathology Ch. 12 Migration and homing in Multiple Myeloma Ch. 13 Genes and proteins of myeloma endothelial cells to search specific targets of the tumor vasculature Ch. 14 Epigenetic regulation of myeloma within its bone marrow microenvironment Ch. 15 Targeting mulitple myeloma tumor angiogenesis: focus on VEGF Ch. 16 Novel in vivo model in myeloma Volume 2 Ch. 1 T cell responses in myeloma Ch. 2 Novel antigenic targets for immunotherapy in myeloma Ch.3 Antibody-based therapies in Multiple Myeloma Ch.4 Defining multiple myeloma as a target for DNA gene fusion vaccines Ch.5 Harnessing allogeneic immunity for anti-myeloma response Ch.6 Dendritic cell and peptide-based vaccination in myeloma Ch.7 New Proteasome inhibitors Ch.8 Newer Imids Ch.9 New agents in myeloma Ch.10 Early Combination Studies in MM Ch.11 The effect of novel antimyeloma agents on bone metabolism