Influence of imatinib mesylate on radiosensitivity of astrocytoma cells.

Imatinib mesylate (STI571), an inhibitor of alpha- and beta-platelet-derived growth factor receptors (PDGFR) and other tyrosine kinases, is a well established treatment for chronic myeloid leukaemia and gastrointestinal stromal tumours. Moreover, it is under investigation for the therapy of several other malignant tumours since protein kinases are frequently mutated or otherwise deregulated in human malignancies and they serve as a target for differentiating between tumour cells and normal tissues. The objective of this study was to determine whether gamma radiation could sensitize astrocytoma cell lines to the effects of imatinib in vitro. For this purpose, T98G and MOG-G-UVW astrocytoma cells were treated with imatinib alone or in combination with gamma radiation. The clonogenic survival assays performed with the combination of imatinib with radiation demonstrated that the drug had an additive antiproliferative effect in both cell lines considered. Imatinib confered greater radiosensitivity on the T98G tumour cells effecting a significant decrease in colony formation compared with radiation alone. These data provide a rationale to further investigate the combination of imatinib with radiation, keeping in mind that this may result in unexpected toxicities that are not observed with either treatment alone.