Tom Baker Cancer Center Assistant Professor University of Calgary Foothills Medical Center
The study of signaling pathways in hematological malignancies and in particular multiple myeloma with the goal of discovering new molecular targets for therapeutic applications. I have been investigating the mechanisms by which arsenic trioxide induces death in multiple myeloma in vitro. These studies have focused on the intracellular mechanisms of arsenicmediated reactive oxygen species generation in the induction of apoptosis, evaluation of the role of the glutathione redox pathway and related enzymes in chemoresistance and the study of glutathione depleting agents in vitro. This research indicated a central role for intracellular glutathione (GSH) in protecting against arsenicinduced death. We have subsequently found that ascorbic acid, as a prooxidant, can deplete intracellular GSH in myeloma cells, resulting in increased arsenic trioxide efficacy. These studies were recently published in BLOOD. These studies were the basis of an NCIsponsored phase I/II clinical trial using arsenic trioxide+ ascorbic acid n refractory/relapsed multiple myeloma. My studies have been extended to clinical samples from this trial. The results of the phase I clinical trial were published in the 2002 December issue of Clinical Cancer Research.
years treating myeloma:
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Lot 1 parkade exit B Eagle Ridge
Calgary, Canada, Canada, T2V2X3
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