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Maruwge W, D'Arcy P, Folin A, et al. Sorafenib inhibits tumor growth and vascularization of rhabdomyosarcoma cells by blocking IGF-1R-mediated signaling. Onco Targets Ther. 2008;1:67-78doi: 10.2147/ott.s3833.
Maruwge, W., D'Arcy, P., Folin, A., Brnjic, S., Wejde, J., Davis, A., Erlandsson, F., Bergh, J., & Brodin, B. (2008). Sorafenib inhibits tumor growth and vascularization of rhabdomyosarcoma cells by blocking IGF-1R-mediated signaling. OncoTargets and therapy, 167-78. https://doi.org/10.2147/ott.s3833
Maruwge, Wessen, et al. "Sorafenib inhibits tumor growth and vascularization of rhabdomyosarcoma cells by blocking IGF-1R-mediated signaling." OncoTargets and therapy vol. 1 (2008): 67-78. doi: https://doi.org/10.2147/ott.s3833
Maruwge W, D'Arcy P, Folin A, Brnjic S, Wejde J, Davis A, Erlandsson F, Bergh J, Brodin B. Sorafenib inhibits tumor growth and vascularization of rhabdomyosarcoma cells by blocking IGF-1R-mediated signaling. Onco Targets Ther. 2008 Nov 01;1:67-78. doi: 10.2147/ott.s3833. PMID: 21127754; PMCID: PMC2994208.
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Onco Targets Ther. 2008 Nov 01;1:67-78. doi: 10.2147/ott.s3833.

Sorafenib inhibits tumor growth and vascularization of rhabdomyosarcoma cells by blocking IGF-1R-mediated signaling.

OncoTargets and therapy

Wessen Maruwge, Pádraig D'Arcy, Annika Folin, Slavica Brnjic, Johan Wejde, Anthony Davis, Fredrik Erlandsson, Jonas Bergh, Bertha Brodin

Affiliations

  1. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

PMID: 21127754 PMCID: PMC2994208 DOI: 10.2147/ott.s3833

Abstract

The growth of many soft tissue sarcomas is dependent on aberrant growth factor signaling, which promotes their proliferation and motility. With this in mind, we evaluated the effect of sorafenib, a receptor tyrosine kinase inhibitor, on cell growth and apoptosis in sarcoma cell lines of various histological subtypes. We found that sorafenib effectively inhibited cell proliferation in rhabdomyosarcoma, synovial sarcoma and Ewing's sarcoma with IC(50) values <5 μM. Sorafenib effectively induced growth arrest in rhabdomyosarcoma cells, which was concurrent with inhibition of Akt and Erk signaling. Studies of ligand-induced phosphorylation of Erk and Akt in rhabdomyosarcoma cells showed that insulin-like growth factor-1 is a potent activator, which can be blocked by treatment with sorafenib. In vivo sorafenib treatment of rhabdomyosarcoma xenografts had a significant inhibitory effect on tumor growth, which was associated with inhibited vascularization and enhanced necrosis in the adjacent tumor stroma. Our results demonstrate that in vitro and in vivo growth of rhabdomyosarcoma can be suppressed by treatment with sorafenib, and suggests the possibilities of using sorafenib as a potential adjuvant therapy for the treatment of rhabdomyosarcoma.

Keywords: kinase inhibitors; soft tissue sarcoma; targeted therapy; vascularization

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