Rekers N H, Sminia P, Peters G J
Department of Medical Oncology, VU University Medical Center, The Netherlands.
J Chemother. 2011 Aug;23(4):187-99. doi: 10.1179/joc.2011.23.4.187.
Gliobastoma multiform (GBM) is the most common and aggressive brain tumor, which is characterized by its infiltrative nature. Current standard therapy for GBMs consists of surgery followed by radiotherapy combined with the alkylating agent temozolomide (TMZ). Recent clinical trials have demonstrated that this chemo-irradiation approach results in a significant increase in survival compared to radiotherapy alone. Nevertheless, due to tumor recurrence, the median survival time is still limited to approximately 15 months. Recently, several studies have focused on aberrant signal transduction in GBM, resistance mechanisms of GBM to TMZ and to radiotherapy. Attention has been focused on molecular targets including phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, protein kinase C (pKC) pathway, Ras/mitogen-activated protein kinase pathway (MAPK), Wnt pathway and intrinsic or extrinsic apoptosis pathways. In addition, research has been directed to radiotherapy and radiosensitizing agents, and cancer gene therapy as well. This article will address several resistance mechanisms of GBM to chemotherapy and radiotherapy and the recent preclinical and clinical studies on targeted therapy.
多形性胶质母细胞瘤（GBM）是最常见且侵袭性最强的脑肿瘤，其特点是具有浸润性。目前GBM的标准治疗方法包括手术，随后进行放疗并联合烷化剂替莫唑胺（TMZ）。最近的临床试验表明，与单纯放疗相比，这种放化疗方法可显著提高生存率。然而，由于肿瘤复发，中位生存时间仍局限于约15个月。最近，多项研究聚焦于GBM中异常的信号转导、GBM对TMZ和放疗的耐药机制。注意力集中在包括磷脂酰肌醇3激酶（PI3K）/Akt信号通路、蛋白激酶C（pKC）通路、Ras/丝裂原活化蛋白激酶通路（MAPK）、Wnt通路以及内在或外在凋亡通路等分子靶点上。此外，研究还涉及放疗和放射增敏剂，以及癌症基因治疗。本文将探讨GBM对化疗和放疗的几种耐药机制以及近期关于靶向治疗的临床前和临床研究。
