system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adaptor Proteins, Signal Transducing, Animals, Benzimidazoles, Cell Growth Processes, Cell Line, Tumor, Enzyme Inhibitors, Humans, Membrane Proteins, Mice, Mice, SCID, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Multiple Myeloma, Phosphorylation, Protein-Tyrosine Kinases, Quinolones, Receptor, Fibroblast Growth Factor, Type 3, Xenograft Model Antitumor Assays.
user
Is cHIR-258 efficacious in a newly developed fibroblast growth factor receptor 3-expressing orthotopic multiple myeloma model in mice? Context: The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) results from a t(4;14) chromosomal translocation that occurs in approximately 15% of multiple myeloma (MM) patients and confers a particularly poor prognosis. This study assesses the antimyeloma activity of CHIR-258, a small-molecule inhibitor of multiple receptor tyrosine kinases that is currently in phase I trials, in a newly developed FGFR3-driven preclinical MM animal model. We developed an orthotopic MM model in mice using a luciferase-expressing human KMS-11-luc line that expresses mutant FGFR3 (Y373C). The antimyeloma activity of CHIR-258 was evaluated at doses that inhibited FGFR3 signaling in vivo in this FGFR3-driven animal model. Noninvasive bioluminescence imaging detected MM lesions in nearly all mice injected with KMS-11-luc cells, which were mainly localized in the spine, skull, and pelvis, resulting in frequent development of paralysis. Daily oral administration of CHIR-258 at doses that inhibited FGFR3 signaling in KMS-11-luc tumors in vivo resulted in a significant inhibition of KMS-11-luc tumor growth, which translated into a significant improvement in animal survival.
assistant
Our data provide a relevant preclinical basis for clinical trials of CHIR-258 in FGFR3-positive MM patients. Final Decision: yes