ArticleOncotarget2016
SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Inhibition of Src signaling induces autophagic killing of Toxoplasma gondii via PTEN-mediated deactivation of Akt.PLoS pathogens · 2025Article
- CD3ζ-Mediated Signaling Protects Retinal Ganglion Cells in Glutamate Excitotoxicity of the Retina.Cells · 2024Article
- Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.Cell death & disease · 2023Article
- Attenuated expression of SNF5 facilitates progression of bladder cancer via STAT3 activation.Cancer cell international · 2021Article
- Targeting thymidine phosphorylase as a potential therapy for bone loss associated with periprosthetic osteolysis.Bioengineering & translational medicine · 2021Article
- Mechanisms of disease-modifying effect of saracatinib (AZD0530), a Src/Fyn tyrosine kinase inhibitor, in the rat kainate model of temporal lobe epilepsy.Neurobiology of disease · 2021Article
- Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva.JCI insight · 2021Article
- Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts.Cancers · 2019Article
- Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts.Blood cancer journal · 2018Article
- Maternal embryonic leucine zipper kinase inhibitor OTSSP167 has preclinical activity in multiple myeloma bone disease.Haematologica · 2018Article
- NS-018 reduces myeloma cell proliferation and suppresses osteolysis through inhibition of the JAK2 and Src signaling pathways.Blood cancer journal · 2018Article
- Maternal embryonic leucine zipper kinase is a novel target for proliferation-associated high-risk myeloma.Haematologica · 2018Article
- Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis.PloS one · 2018Article
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15 authors.
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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.
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