Sathornsumetee Sith, Rich Jeremy N
Neuro-Oncology Program, Departments of Medicine (Neurology) and Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Ann N Y Acad Sci. 2008 Oct;1142:108-32. doi: 10.1196/annals.1444.009.
Primary brain tumors account for less than 2% of all cancers in adults; however, they are often associated with neurologic morbidity and high mortality. Glioblastoma multiforme (GBM) has been a focus of new therapy development in neurooncology because it is the most common primary brain tumor in adults. Standard-of-care therapy for newly diagnosed GBM includes surgical resection, radiotherapy, and temozolomide, administered both during and after radiotherapy. However, most patients develop tumor recurrence or progression after this multimodality treatment. Repeat resection and stereotactic radiosurgery upon recurrence may improve outcome only in selected patients. Most salvage chemotherapies offer only palliation. Recent advances in our understanding of the molecular abnormalities of GBM have generated new therapeutic venues of molecularly targeted agents (designer drugs) against key components of cellular pathways critical for cancer initiation and maintenance. Such drugs may offer the potential advantage to increase therapeutic efficacy and decrease systemic toxicity compared with traditional cytotoxic agents. Nonetheless, first-generation targeted agents have failed to demonstrate survival benefits in unselected GBM patient populations. Several mechanisms of treatment failure of the first-generation designer drugs have been proposed, whereas new strategies have been developed to increase effectiveness of these agents. Here we will discuss the recent development and the strategies to optimize the effectiveness of designer therapy for GBM.
原发性脑肿瘤在成人所有癌症中所占比例不到2%；然而，它们常与神经功能障碍和高死亡率相关。多形性胶质母细胞瘤（GBM）一直是神经肿瘤学新疗法开发的重点，因为它是成人中最常见的原发性脑肿瘤。新诊断GBM的标准治疗方法包括手术切除、放疗以及在放疗期间和放疗后使用替莫唑胺。然而，大多数患者在这种多模式治疗后会出现肿瘤复发或进展。复发时重复切除和立体定向放射外科手术可能仅对部分患者的预后有改善作用。大多数挽救性化疗仅能起到缓解作用。我们对GBM分子异常认识的最新进展催生了针对对癌症起始和维持至关重要的细胞通路关键成分的分子靶向药物（定制药物）的新治疗途径。与传统细胞毒性药物相比，这类药物可能具有提高治疗效果和降低全身毒性的潜在优势。尽管如此，第一代靶向药物在未经过挑选的GBM患者群体中未能显示出生存获益。已经提出了第一代定制药物治疗失败的几种机制，同时也开发了新的策略来提高这些药物的有效性。在此，我们将讨论GBM定制治疗的最新进展以及优化其有效性的策略。
