Dr. Senckenberg Institute of Neurooncology, Center of Neurology and Neurosurgery, Goethe-University Hospital, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany.
Target Oncol. 2010 Sep;5(3):183-91. doi: 10.1007/s11523-010-0154-5. Epub 2010 Sep 19.
Despite advances in the understanding of the molecular biology of glioblastomas (GB), these neoplasms still are incurable with conventional therapies. Current efforts therefore focus on the development of new molecular approaches that exploit the genetic aberrations of cancer cells. Based on their frequent activation or mutation in human GB and their paramount role for the maintenance of the neoplastic phenotype, both the epidermal growth factor receptor (EGFR) and the mammalian target of rapamycin (mTOR) are plausible targets for molecular therapies. However, clinical trials with drugs targeting EGFR or mTOR, so far, have produced largely disappointing results. In this article, we review strategies targeting EGFR and mTOR as therapies for malignant glioma. Recent advances in the understanding of the complex signaling network involved are highlighted and the results of clinical trials are summarized. Mechanisms of resistance are explored, and potential future directions as well as trends in preclinical and clinical development are discussed.
尽管人们对胶质母细胞瘤（GB）的分子生物学有了更深入的了解，但这些肿瘤仍然无法通过常规疗法治愈。因此，目前的研究重点是开发新的分子方法，利用癌细胞的遗传异常。基于其在人类 GB 中的频繁激活或突变，以及其对维持肿瘤表型的至关重要的作用，表皮生长因子受体（EGFR）和哺乳动物雷帕霉素靶蛋白（mTOR）都是分子治疗的合理靶点。然而，迄今为止，针对 EGFR 或 mTOR 的药物临床试验的结果大多令人失望。本文综述了针对 EGFR 和 mTOR 的治疗策略作为治疗恶性胶质瘤的方法。强调了对涉及的复杂信号网络的最新理解，并总结了临床试验的结果。探讨了耐药机制，并讨论了潜在的未来方向以及临床前和临床开发的趋势。
