Thomas Reena P, Recht Lawrence, Nagpal Seema
Department of Neurological Sciences, Stanford University Hospital, Stanford, CA, USA.
Clin Pharmacol. 2013;5:1-9. doi: 10.2147/CPAA.S26586. Epub 2012 Dec 27.
Glioblastoma (GB) is one of the most lethal forms of cancer, with an invasive growth pattern that requires the use of adjuvant therapies, including chemotherapy and radiation, to prolong survival. Temozolomide (TMZ) is an oral chemotherapy with a limited side effect profile that has become the standard of care in GB treatment. While TMZ has made an impact on survival, tumor recurrence and TMZ resistance remain major challenges. Molecular markers, such as O6-methylguanine-DNA methyltransferase methylation status, can be helpful in predicting tumor response to TMZ, and therefore guides clinical decision making. This review will discuss the epidemiology and possible genetic underpinnings of GB, how TMZ became the standard of care for GB patients, the pharmacology of TMZ, the practical aspects of using TMZ in clinic, and how molecular diagnostics - particularly the use of O6-methylguanine-DNA methyltransferase status - affect clinical management.
胶质母细胞瘤(GB)是最致命的癌症形式之一,其侵袭性生长模式需要使用包括化疗和放疗在内的辅助治疗来延长生存期。替莫唑胺(TMZ)是一种口服化疗药物,副作用有限,已成为GB治疗的标准疗法。虽然TMZ对生存期有影响,但肿瘤复发和TMZ耐药性仍然是主要挑战。分子标志物,如O6-甲基鸟嘌呤-DNA甲基转移酶甲基化状态,有助于预测肿瘤对TMZ的反应,从而指导临床决策。本综述将讨论GB的流行病学和可能的遗传基础、TMZ如何成为GB患者的标准治疗方法、TMZ的药理学、在临床中使用TMZ的实际情况,以及分子诊断——特别是O6-甲基鸟嘌呤-DNA甲基转移酶状态的使用——如何影响临床管理。