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Sydney 2005: CHIR-258, a Novel Multi-Targeted Tyrosine Kinase Inhibitor, for the Tx of t(4;14) MM
By Suzanne Trudel
Dr. Trudel presented on another novel agent, CHIR-258, a multi-targeted tyrosine kinase inhibitor in the treatment of t(4;14) MM. Approximately 15% of patients with MM have a unique t(4;14) translocation, which results in the expression of a receptor tyrosine kinase known as fibroblast growth factor receptor3 (FGFR3). Patients with t(4;14) translocations have a poor prognosis despite use of high-dose chemotherapy highlighting the need for a new therapeutic agent that may improve the clinical outcomes of patients in this subset. Given this information, Dr. Trudel’s studies hypothesized that the inhibition of FGFR3 kinase activity will prevent tumor formation. CHIR-258 is a potent inhibitor of class III, IV, and V receptor tyrosine kinases (RTK). An in vitro analysis of CHIR-258 in combination with dexamethasone applied to MM cells demonstrated a synergistic interaction. In vivo, CHIR-258 induced tumor regression and inhibited growth of FGFR3 tumors in mouse model. In MM samples from patients with this translocation, CHIR-258 produced cytotoxic responses. She ended her presentation stating a Phase 1 trial will be initiated shortly in the United States and the United Kingdom.

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