CDK4/6抑制剂在治疗脑胶质母细胞瘤中的研究进展

Research progress in CDK4/6 inhibitors in the treatment of glioblastoma

细胞周期素依赖性蛋白激酶在临床上已用于乳腺癌的治疗,其机制是促使抑癌基因Rb磷酸化,使细胞从G1期进入S期。CDK4/6抑制剂可以抑制乳腺癌、头颈癌、非小细胞肺癌等多种恶性肿瘤的活性。胶质母细胞瘤具有复发率高、生存期短、预后差等特点,治疗难度大,而CDK4/6理论上作为胶质母细胞瘤(GBM)治疗的靶点,CDK4/6抑制剂作用于cyclin D-CDK4/6-INK4-Rb通路,也同样可以抑制胶质母细胞瘤。作为有希望治疗胶质母细胞瘤药物,CDK4/6抑制剂在动物实验,肿瘤细胞系等研究中展示了大量的证据证明其对胶质母细胞瘤能产生抑制作用。同时CDK4/6抑制剂其研发方向是寻找预测标志物,探索联合治疗,以试图解决神经胶质母细胞瘤治疗中的耐药性和复发性中的关键问题,为治疗神经胶质瘤的研究提供新方向和思路。

Cyclin-dependent protein kinase(CDK)has been clinically applied in the treatment of breast cancer,which promotes the phosphorylation of tumor suppressor gene Rb and enables cells to enter the S phase from the G1 phase.CDK4/6 inhibitors can inhibit the activity of breast cancer,head and neck cancer,non-small cell lung cancer,and other malignant tumors.Glioblastoma has the characteristics of high recurrence rate,short survival time,and poor prognosis,which makes it difficult to treat.CDK4/6 is theoretically the target of glioblastoma treatment.CDK4/6 inhibitors act on one of the three classical pathways—the cyclin D-CDK4/6-INK4-Rb pathway,and also can inhibit glioblastoma.As promising drugs for the treatment of glioblastoma,CDK4/6 inhibitors have proved their inhibitory effects on glioblastoma,according to a large amount of evidence from animal experiments and tumor cell line and other studies.The development direction of CDK4/6 inhibitors is to search for predictive markers and to explore combined treatment to try to solve the key problems of drug resistance and recurrence in the treatment of glioblastoma,and to provide new directions and ideas for the treatment of glioblastoma.