Molecular Targets for the Treatment of Multiple Myeloma

Marco      Rossi; Maria      Teresa Di Martino; Eugenio      Morelli; Marzia      Leotta; Antonietta      Rizzo; Anna      Grimaldi; Gabriella      Misso; Pierfrancesco      Tassone; Michele      Caraglia

doi:10.2174/156800912802429300

Abstract

Multiple myeloma (MM) represents a suitable disease to be treated with Molecularly targeted drugs (MTDs). MM clone aberrations affect signal transduction pathways controlling both proliferation and/or cell survival. Research findings on small drugs or monoclonal antibodies (mAb) against the components of these pathways are now available and related clinical trials in MM patients are rapidly growing up. Promising results have been recently obtained with AKT inhibitors (perifosine) and mTOR inhibitors (everolimus and temsirolimus). However, the activity of these agents used alone is still limited and can be strongly increased by their combination with other drugs such as bortezomib or dexamethasone. The present review will summarize the main signaling components that can be targeted by MTDs and the most important available results derived from the clinical trials based on their use. Another important issue in the treatment of MM is the control of the related bone disease. Two main strategies can be used: i) inhibition of bone resorption and ii) promotion of bone formation. Emerging clinical data suggest that specific MTDs are able to prolong survival not only for the prevention of the skeletal-related events but also for a direct or indirect effect on the proliferation and/or survival of MM cells. A summary on the main preclinical and clinical results in this setting will be provided. In conclusion, the use of MTD in the treatment of MM is a promising approach but still far from becoming a current indication: a new dawn is arising with still unpredictable results.

Keywords: Bone disease, epigenetic therapy, molecular pathway, monoclonal antibodies, multiple myeloma, target therapy, eIF-4E-binding protein 1, Aurora kinases, Chromosomal passenger complex, Disease free survival, Bone marrow stromal cells, B cell activating factor, Macrophage inflammatory Protein Immunomodulatory drugs.