Puduvalli Vinay K, Chaudhary Rekha, McClugage Samuel G, Markert James
From The Ohio State University Comprehensive Cancer Center, Columbus, OH; University of Cincinnati, Cincinnati, OH; University of Alabama at Birmingham, Birmingham, AL.
Am Soc Clin Oncol Educ Book. 2017;37:175-186. doi: 10.1200/EDBK_175003.
Recent advances in therapies have yielded notable success in terms of improved survival in several cancers. However, such treatments have failed to improve outcome in patients with gliomas for whom surgery followed by radiation therapy and chemotherapy with alkylating agents remain the standard of care. Genetic and epigenetic studies have helped identify several alterations specific to gliomas. Attempts to target these altered pathways have been unsuccessful due to various factors, including tumor heterogeneity, adaptive resistance of tumor cells, and limitations of access across the blood-brain barrier. Novel therapies that circumvent such limitations have been the focus of intense study and include approaches such as immunotherapy, targeting of signaling hubs and metabolic pathways, and use of biologic agents. Immunotherapeutic approaches including tumor-targeted vaccines, immune checkpoint blockade, antibody-drug conjugates, and chimeric antigen receptor-expressing cell therapies are in various stages of clinical trials. Similarly, identification of key metabolic pathways or converging hubs of signaling pathways that are tumor specific have yielded novel targets for therapy of gliomas. In addition, the failure of conventional therapies against gliomas has led to a growing interest among patients in the use of alternative therapies, which in turn has necessitated developing evidence-based approaches to the application of such therapies in clinical studies. The development of these novel approaches bears potential for providing breakthroughs in treatment of more meaningful and improved outcomes for patients with gliomas.
近年来，治疗方法的进展在提高多种癌症患者的生存率方面取得了显著成功。然而，对于胶质瘤患者，此类治疗未能改善其预后，目前胶质瘤的标准治疗仍是手术，随后进行放射治疗和使用烷化剂的化疗。基因和表观遗传学研究有助于识别胶质瘤特有的几种改变。由于多种因素，包括肿瘤异质性、肿瘤细胞的适应性耐药以及血脑屏障的限制，针对这些改变的通路进行靶向治疗一直未成功。规避这些限制的新型疗法一直是深入研究的重点，包括免疫疗法、靶向信号枢纽和代谢通路以及使用生物制剂等方法。免疫治疗方法，包括肿瘤靶向疫苗、免疫检查点阻断、抗体药物偶联物和嵌合抗原受体表达细胞疗法，正处于临床试验的不同阶段。同样，识别肿瘤特异性的关键代谢通路或信号通路的汇聚枢纽，为胶质瘤治疗产生了新的靶点。此外，针对胶质瘤的传统疗法的失败导致患者对使用替代疗法的兴趣日益增加，这反过来又需要在临床研究中开发基于证据的方法来应用此类疗法。这些新方法的开发有可能为胶质瘤患者带来更有意义的治疗突破和改善预后。
