Related Experiment Video
Updated: Aug 6, 2026
Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
Published on: May 1, 2015
CHIR-258 is efficacious in a newly developed fibroblast growth factor receptor 3-expressing orthotopic multiple
Xiaohua Xin1, Tinya J Abrams, Paul W Hollenbach
1Translational Sciences, Chiron Corporation, Emeryville, California, USA.
Purpose:
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.
Experimental Design:
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.
Results:
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.
Conclusions:
Our data provide a relevant preclinical basis for clinical trials of CHIR-258 in FGFR3-positive MM patients.
Insights
CHIR-258 effectively inhibited multiple myeloma (MM) tumor growth and improved survival in a preclinical model. This FGFR3 inhibitor shows promise for treating patients with FGFR3-positive MM.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Fibroblast growth factor receptor 3 (FGFR3) deregulation due to t(4;14) translocation occurs in 15% of multiple myeloma (MM) patients.
- FGFR3-driven MM is associated with a poor prognosis.
- Targeting FGFR3 is a potential therapeutic strategy for MM.
Purpose of the Study:
- To assess the antimyeloma activity of CHIR-258, a multi-receptor tyrosine kinase inhibitor.
- To evaluate CHIR-258 in a newly developed preclinical model of FGFR3-driven MM.
Main Methods:
- An orthotopic multiple myeloma (MM) mouse model was established using KMS-11-luc cells expressing mutant FGFR3 (Y373C).
- Noninvasive bioluminescence imaging was used to monitor MM lesions.
- CHIR-258 was administered orally at doses inhibiting FGFR3 signaling in vivo.
Main Results:
- KMS-11-luc cells formed MM lesions in mice, primarily in the spine, skull, and pelvis, leading to paralysis.
- CHIR-258 treatment significantly inhibited KMS-11-luc tumor growth.
- CHIR-258 administration led to a significant improvement in animal survival.
Conclusions:
- CHIR-258 demonstrated significant antimyeloma activity in a preclinical FGFR3-driven MM model.
- These findings provide a preclinical rationale for investigating CHIR-258 in clinical trials for FGFR3-positive MM patients.
