Sunitinib malate (SU-11248) reduces tumour burden and lung metastasis in an intratibial human xenograft osteosarcoma mouse model.
Osteosarcoma is a rare type of cancer that commonly occurs as a primary bone tumour in children and adolescents and is associated with a poor clinical outcome. Despite complex treatment protocols, including chemotherapy combined with surgical resection, the prognosis for patients with osteosarcoma and metastases remains poor and more effective therapies are required. In this study, we evaluated the therapeutic efficacy of sunitinib malate, a wide-spectrum tyrosine kinase inhibitor, in a preclinical mouse model of osteosarcoma. Sunitinib significantly inhibited proliferation, provoked apoptosis and induced G2/M cell cycle arrest in the human osteosarcoma cell lines SaOS-2 and 143B in vitro. Importantly, sunitinib treatment significantly reduced tumour burden, microvessel density and suppressed pulmonary metastasis in a 143B cell-derived intratibial osteosarcoma model in SCID mice. Sunitinib significantly decreased primary tumor tissue proliferation and reduced tumor vasculature. Our study indicates that sunitinib has potential for effective treatment of metastasizing osteosarcoma and provides the framework for future clinical trials with sunitinib alone or in combination with conventional and other novel therapeutics aiming at increased treatment efficacy and improved patient outcome.
Department of Orthopaedics, Laboratory for Orthopaedic Research, Balgrist University Hospital, University of Zurich Zurich, Switzerland.
Ram Mohan Ram
RM
Kumar
Department of Orthopaedics, Laboratory for Orthopaedic Research, Balgrist University Hospital, University of Zurich Zurich, Switzerland.
Matthias Je
MJ
Arlt
Department of Orthopaedics, Laboratory for Orthopaedic Research, Balgrist University Hospital, University of Zurich Zurich, Switzerland.
Aleksandar
A
Kuzmanov
Department of Orthopaedics, Laboratory for Orthopaedic Research, Balgrist University Hospital, University of Zurich Zurich, Switzerland.
Walter
W
Born
Department of Orthopaedics, Laboratory for Orthopaedic Research, Balgrist University Hospital, University of Zurich Zurich, Switzerland.
Bruno
B
Fuchs
Osteosarcoma; intratibial; lung metastasis; microvessel; sunitinib malate; tyrosine kinase inhibitor