Platelet-derived growth factor receptor as a prognostic marker and a therapeutic target for imatinib mesylate therapy in osteosarcoma (pages 2119–2129)
Tadahiko Kubo, Sajida Piperdi, Jeremy Rosenblum, Cristina R. Antonescu, Wen Chen, Han-Soo Kim, Andrew G. Huvos, Rebecca Sowers, Paul A. Meyers, John H. Healey and Richard Gorlick
Article first published online: 13 MAR 2008 | DOI: 10.1002/cncr.23437
To determine the role of imatinib mesylate (STI571, Gleevec) in the treatment of osteosarcoma, the expression of platelet-derived growth factor (PDGF) receptor and its ligand was examined in osteosarcoma patient specimens and related to prognosis. The effects of imatinib mesylate on growth and molecular events in osteosarcoma primary cultures were investigated. Immunohistochemical studies demonstrated frequent expression of PDGF receptor and its ligand and their correlation with inferior event-free survival (P < .05). In vitro studies demonstrated that imatinib mesylate had a variable cytotoxic effect on various osteosarcoma primary cultures and blocked the PDGF-induced intracellular signal transduction as well as the inhibition of downstream Akt phosphorylation. Mitogen-activated protein kinase (MAPK) was constitutively activated despite PDGF stimulation.