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.

中文翻译：

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BMS-536924是一种具有ATP竞争性的IGF-1R / IR抑制剂，在体外可降低耐替莫唑胺类神经胶质瘤细胞的活力和迁移，并在体内抑制肿瘤的生长。

胶质瘤是最常见的原发性脑肿瘤类型。尽管手术，化学疗法和放射疗法相结合，恶性神经胶质瘤患者的中位生存期仍然很短。替莫唑胺（TMZ）是神经胶质瘤的主要和最有前途的治疗药物。但是，在治疗过程中很容易产生获得性抗药性。受体酪氨酸激酶（RTKs）的激活已被确定与许多抗癌药物产生抗药性有关。因此，抑制RTK可能是克服或减弱获得性耐药的一种有前途的治疗策略。在这里，我们研究了BMS-536924（一种具有ATP竞争性的IGF-1R / IR抑制剂）在神经胶质瘤（尤其是TMZ耐药性神经胶质瘤）中的体内外抗癌活性。我们发现BMS-536924可以有效降低TMZ敏感性和耐药性神经胶质瘤细胞的活力。BMS-536924在TMZ耐药细胞中诱导了戏剧性的细胞凋亡，并且还显着抑制了TMZ耐药细胞的迁移。重要的是，BMS-536924在体内显着抑制了神经胶质瘤的生长。这是关于BMS-536924在神经胶质瘤中的抗癌活性的首次报道。BMS-536924是治疗神经胶质瘤，尤其是对TMZ耐药的神经胶质瘤的有前途的化合物，可能为神经胶质瘤的治疗提供新的思路。这是关于BMS-536924在神经胶质瘤中的抗癌活性的首次报道。BMS-536924是治疗神经胶质瘤，尤其是对TMZ耐药的神经胶质瘤的一种有前途的化合物，可能为神经胶质瘤的治疗提供新的思路。这是关于BMS-536924在神经胶质瘤中的抗癌活性的首次报道。BMS-536924是治疗神经胶质瘤，尤其是对TMZ耐药的神经胶质瘤的一种有前途的化合物，可能为神经胶质瘤的治疗提供新的思路。