Journal
ONCOTARGETS AND THERAPY
Volume 8, Issue -, Pages 689-697Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S80047
Keywords
resistance; proliferation; motility; brain tumor resistance
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Glioma is the most common type of primary brain tumor. Despite the combination of surgery, chemotherapy, and radiotherapy, the median survival duration of patients with malignant glioma is still very short. Temozolomide (TMZ) is the primary and most promising therapeutic drug for glioma; however, it is easy to develop acquired resistance during treatment. Activation of receptor tyrosine kinases (RTKs) has been identified to be involved in the acquisition of resistance toward many anticancer drugs. So inhibition of RTKs might be a promising therapeutic strategy for overcoming or attenuating acquired drug resistance. Here, we have investigated the anticancer activities of BMS-536924, an ATP-competitive IGF-1R/IR inhibitor in glioma, especially TMZ-resistant glioma, both in vitro and in vivo. We found that BMS-536924 could effectively reduce viability of both TMZ-sensitive and -resistant glioma cells. BMS-536924 induced dramatic apoptosis in TMZ-resistant cells, and it also dramatically inhibited migration of TMZ-resistant cells. Importantly, BMS-536924 significantly suppressed glioma tumor growth in vivo. This is the first report on anticancer activity of BMS-536924 in glioma. BMS-536924 is a promising compound in the therapy of glioma, especially of TMZresistant glioma, which might shed new light on glioma therapy.
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