Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH.
Onco Targets Ther. 2013 Apr 15;6:371-89. doi: 10.2147/OTT.S38628. Print 2013.
High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV) are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas.
尽管在理解分子遗传学、信号通路、细胞骨架动力学以及干细胞在胶质瘤发生中的作用方面取得了进展，但高级别神经胶质瘤的预后仍然不佳。传统的治疗方法，包括手术、放疗和细胞毒性化疗，已经取得了一定的成功。然而，使用分子靶向治疗、免疫治疗和其他方法（如饮食治疗）的治疗进展尚未能够阻止肿瘤进展和与疾病相关的死亡。高级别神经胶质瘤（世界卫生组织分级 III/IV）在组织学上的特征是细胞和核异型性、新生血管形成和坏死。血管内皮生长因子是一种分子介质，其表达在血管增殖和肿瘤存活中起着关键作用。针对血管内皮生长因子的靶向治疗已经显示出了令人鼓舞的结果，改善了生活质量和无进展生存期。贝伐单抗是一种针对血管内皮生长因子的人源化单克隆抗体，已被美国食品和药物管理局批准作为复发性胶质母细胞瘤的单一药物，并且具有可管理的毒性。本文讨论了贝伐单抗在高级别神经胶质瘤治疗中的疗效、实际应用和反应评估方面的挑战。
