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 TMZ-resistant
glioma, which might shed new light on
glioma therapy.