Cancer Cell - Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis - Sunitinib/SU11248

definition: orthotopic = in the normal position

Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis

John M.L. Ebos,Christina R. Lee,William Cruz-Munoz,Georg A. Bjarnason,James G. Christensen and Robert S. Kerbel1
Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, Canada
Sunnybrook Odette Cancer Centre, Toronto, ON M5G 2M9, Canada
Pfizer Global Research and Development, La Jolla Labs, La Jolla, CA 92121, USA

Summary

Herein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also observed in mice receiving sunitinib prior to intravenous implantation of tumor cells, suggesting possible metastatic conditioning in multiple organs. Similar findings with additional VEGF receptor tyrosine kinase inhibitors implicate a class-specific effect for such agents. Importantly, these observations of metastatic acceleration were in contrast to the demonstrable antitumor benefits obtained when the same human breast cancer cells, as well as mouse or human melanoma cells, were grown orthotopically as primary tumors and subjected to identical sunitinib treatments.