Westphal Manfred, Lamszus Katrin
Department of Neurosurgery, University Hospital Hamburg Eppendorf, Martinistrasse 52, Hamburg 20251, Germany.
Recent Results Cancer Res. 2009;171:155-64. doi: 10.1007/978-3-540-31206-2_9.
Experimental therapies for glioma are mostly based on the insights into the cell biology of the tumors studied by modern methods including genomics and metabolomics. In surgery, intraoperative visualization of residual tumor by fluorescence has helped with the radicality of resection. Although temozolamide has become an important agent in the combined radiochemotherapy of newly diagnosed glioblastoma, understanding the underlying mechanisms of action and resistance has led to alterations in dosing schemes, which may be more beneficial than the introduction of new agents. Targeted therapies that have been highly promising in other solid tumors have been rather disappointing in gliomas, not for the lack of promising targets but most likely due to inefficacy of the reagents to reach their target. Direct delivery of reagents with interstitial infusion via convection-enhanced delivery has proven to be safe and effective, but the potential of that technology has not been exploited because many technicalities are still to be worked out, and better, more selective reagents are needed. Gene therapy has been reactivated with direct adeno-viral application to transfer HSV-Tk into tumor cells by adenoviral vectors, still awaiting final analysis. Oncolytic viruses are also under long-term refinement and await definitive pivotal clinical trials. Immunotherapy is currently focusing on vaccination strategies using either specifically pulsed dendritic cells or immunization with a specific peptide, which is unique to the vIII variant of the epidemal growth factor receptor. An area attracting immense attention for basic research as well as translation into clinical use is the characterization of neural stem cells and their theraputic potential when appropriately manipulated.In general, there is a wide spectrum of specific neuro-oncological therapy developments, which are not only extrapolated from general oncology but also based on translational research in the field of glioma biology.
胶质瘤的实验性治疗大多基于通过包括基因组学和代谢组学在内的现代方法对肿瘤细胞生物学的深入了解。在手术中,通过荧光对残留肿瘤进行术中可视化有助于提高切除的彻底性。尽管替莫唑胺已成为新诊断胶质母细胞瘤联合放化疗中的重要药物,但对其作用和耐药的潜在机制的了解导致了给药方案的改变,这可能比引入新药物更有益。在其他实体瘤中前景广阔的靶向治疗在胶质瘤中却相当令人失望,这并非因为缺乏有前景的靶点,很可能是由于试剂无法有效到达靶点。通过对流增强递送进行间质内输注直接递送试剂已被证明是安全有效的,但该技术的潜力尚未得到充分利用,因为仍有许多技术细节有待解决,并且需要更好、更具选择性的试剂。基因治疗通过腺病毒载体直接应用腺病毒将单纯疱疹病毒胸苷激酶(HSV-Tk)导入肿瘤细胞而重新启动,仍在等待最终分析。溶瘤病毒也在进行长期改进,等待确定性的关键临床试验。免疫疗法目前主要集中在使用特异性脉冲树突状细胞的疫苗接种策略或用表皮生长因子受体vIII变体特有的特定肽进行免疫接种。一个在基础研究以及转化为临床应用方面都备受关注的领域是神经干细胞的特征及其在适当操作下的治疗潜力。总的来说,有广泛的特定神经肿瘤治疗方法正在发展,这些方法不仅是从一般肿瘤学中推断出来的,也是基于胶质瘤生物学领域的转化研究。