Multiple myeloma: Implementing signaling pathways and molecular biology in clinical trials.

Multiple Myeloma is a molecularly heterogeneous disease with a high degree of genomic instability in which specific genetic changes can be linked to clinical presentation and prognosis. Despite recent improvements in event-free survival and overall survival with the use of high dose chemotherapy and stem cell support as well as the development of novel agents such as thalidomide, lenalidomide and Bortezomib, MM remains an incurable disease. The development of effective targeted therapies requires a detailed knowledge of various genetic and signaling pathways governing MM genesis. This review will focus on the current understanding of the molecular pathogenesis of MM and the intracellular signaling pathways and their regulations, with emphasis on the rationale for identifying therapeutic targets that can be applied in the clinic.