Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202, USA.
Expert Rev Neurother. 2011 Apr;11(4):509-18. doi: 10.1586/ern.11.37.
The management of recurrent high-grade gliomas with conventional, as well as targeted, therapies is problematic owing to several confounding issues. First, the diagnosis of recurrence using MRI is not straightforward, making the assessment of images in daily routines, as well as in clinical trials, challenging. While chemotherapies with cytotoxic agents have demonstrated initial treatment response, most tumors recur quickly. Second, targeted therapy itself is confounded by the heterogeneous expression of drug targets and nonlinear signaling effects, with functional redundancy and sidestream feedback mechanisms resulting in treatment failure; however, several active agents have been identified, most notably, bevacizumab (an antibody that sequesters VEGF), cilengitide (an inhibitor of integrin αvβ3/5 signaling) and cediranib (an oral tyrosine kinase inhibitor targeting PDGF receptor, c-Kit and all VEGF receptor subtypes). All of these agents have undergone multiple clinical trials and have demonstrated benefits and progression-free survival prolongation in recurrent disease. Given these advances, it is likely that tailored therapies for tumors harboring specific signaling defects will become more efficient and successful in the management of glioblastoma.
由于存在一些复杂的问题，常规治疗和靶向治疗复发性高级别神经胶质瘤的管理存在问题。首先，使用 MRI 诊断复发并不简单，这使得日常工作中的图像评估以及临床试验中的评估变得具有挑战性。虽然细胞毒性药物的化疗显示出初始治疗反应，但大多数肿瘤很快复发。其次，靶向治疗本身受到药物靶点异质性表达和非线性信号效应的干扰，功能冗余和旁流反馈机制导致治疗失败；然而，已经确定了几种活性药物，尤其是贝伐单抗（一种隔离 VEGF 的抗体）、西仑替尼（一种整合素αvβ3/5 信号抑制剂）和 Cediranib（一种针对 PDGF 受体、c-Kit 和所有 VEGF 受体亚型的口服酪氨酸激酶抑制剂）。所有这些药物都经过了多次临床试验，并在复发性疾病中显示出益处和无进展生存期延长。鉴于这些进展，针对携带特定信号缺陷的肿瘤的定制治疗可能在胶质母细胞瘤的管理中更有效和成功。
