My area of research concerns new drug development for the treatment of mature B cell malignancies based on molecular targets. This encompasses drug discovery and pharmacological profiling of candidate compounds, pre-clinical studies to validate the target and determine potential therapeutic mechanisms of action, the establishment of appropriate animal models for drug testing, and the development of Phase I/II clinical trials. Chromosomal translocations are present in approximately 50% of multiple myeloma patients and probably represent the first and defining genetic event that leads to the development of this disease. Characterization of these translocations has led to the identification of critical dysregulated oncogenes (FGFR3 and MMSET, c-maf and mafB, cyclin D1 and D3) that are potential molecular targets for anti-cancer agents. We have recently validated FGFR3 as molecular therapeutic target in t(4;14) myeloma and have identified CHIR-258 as an active drug against FGFR3 expressing myeloma cells in pre-clinical studies. We are about to launch the first ever, clinical trial of FGFR3 inhibition in myeloma and are focusing our efforts on the development and implementation of relevant biological endpoints for this novel class of anti-tumor drug. Validation of additional molecular targets in myeloma such as MMSET and the maf and cyclin family of genes is also under development.
Princess Margaret Cancer Center:
610 University Ave, Toronto, ON M5G 2C4, Canada
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