Title: SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma
Authors: Heusschen, Roy ×
Muller, Joséphine
Binsfeld, Marilène
Marty, Caroline
Plougonven, Erwan
Dubois, Sophie
Mahli, Nadia
Moermans, Karen
Carmeliet, Geert
Léonard, Angélique
Baron, Frédéric
Beguin, Yves
Menu, Eline
Cohen-Solal, Martine
Caers, Jo #
Issue Date: May-2016
Series Title: Oncotarget vol:7 issue:21
Article number: 10.18632/oncotarget.8750
Abstract: Multiple myeloma (MM)-associated osteolytic bone disease is a major cause of morbidity and mortality in MM patients and the development of new therapeutic strategies is of great interest. The proto-oncogene SRC is an attractive target for such a strategy. In the current study, we investigated the effect of treatment with the SRC inhibitor saracatinib (AZD0530) on osteoclast and osteoblast differentiation and function, and on the development of MM and its associated bone disease in the 5TGM.1 and 5T2MM murine MM models. In vitro data showed an inhibitory effect of saracatinib on osteoclast differentiation, polarization and resorptive function. In osteoblasts, collagen deposition and matrix mineralization were affected by saracatinib. MM cell proliferation and tumor burden remained unaltered following saracatinib treatment and we could not detect any synergistic effects with drugs that are part of standard care in MM. We observed a marked reduction of bone loss after treatment of MM-bearing mice with saracatinib as reflected by a restoration of trabecular bone parameters to levels observed in naive control mice. Histomorphometric analyses support that this occurs through an inhibition of bone resorption. In conclusion, these data further establish SRC inhibition as a promising therapeutic approach for the treatment of MM-associated osteolytic bone disease.
ISSN: 1949-2553
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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