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Sydney 2005:
Drug Resistance in Multiple Myeloma
By Pieter Sonneveld
Dr. Sonneveld chaired and opened this session with his presentation on drug resistance in MM. Regardless of the advent of new therapeutic options in the treatment of MM, recurring disease is the primary reason for treatment failure. Multiple factors contribute to variations in drug response, such as drug transport, intracellular signaling, unknown genes, cross talk, and the genetic evolution of the tumor. Therefore, a new strategy focusing on tumor targets needs to be employed to manage drug resistance. Dr. Sonneveld reviewed the role of pharmacogenetics in drug metabolism and reiterated that genetic markers are predictive of patient response to chemotherapy. As mentioned in other presentations, activation of specific signaling pathways may induce cell proliferation and induce apoptosis thereby protecting the MM cell from drug-induced cytotoxicity. Other recently developed drugs target the interaction of the MM cell with the bone marrow microenvironment by inhibiting angiogenesis (thalidomide, lenalidomide) or through downregulation of adhesion molecules (bortezomib). Dr. Sonneveld acknowledged that the mechanisms of drug resistance with these new agents are unknown and there are many issues to overcome due to the complexness of drug resistance.

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