Westphal Manfred, Black Peter McL
Department of Neurosurgery, University Hospital Hamburg Eppendorf, Hamburg, Germany.
J Neurooncol. 2004 Nov;70(2):255-69. doi: 10.1007/s11060-004-2754-3.
Therapeutic efforts for human glial tumors have over the past years been redirected towards a compartmental treatment concept. The diffusely infiltrative nature of the disease calls for therapeutic agents to reach single cells far beyond the focus of attention which present therapies like surgery and radiation are able to treat. Specific drug discovery approaches which seek to define targets which are specific for gliomas have generated therapeutic options which allow for a highly selective development of new reagents. Combined with new modalities for compartmental drug delivery, systemic complications might be reduced and advantage taken of a compartmental specificity of a target which otherwise in the context of systemic application would not be as specific or burdened with side effects. From the present status of therapeutic developments in neuro-oncology it can be expected that a sufficient number of drug targets emerge which can be exploited by means of interstitial or intracavitary delivery, which are not neurotoxic and which may even be imaged in their action with the new metabolic imaging modalities. Convection enhanced delivery, conditionally replicating oncolytic viruses and motile, genetically engineered neural stem cells all seem to fulfill the distribution requirements which an effective therapeutic for gliomas will need to overcome the very limited efficacy which surgery, conventional chemotherapy and radiation have to offer. Whereas the genomics based discovery approaches are not specific for neuro-oncology, the development of delivery strategies is highly specific for the central nervous system, thus creating a unique set of organ and disease specific therapies.
在过去几年中,针对人类胶质细胞瘤的治疗工作已转向分区治疗概念。该疾病的弥漫浸润性要求治疗药物能够作用于远离当前手术和放疗等治疗手段所关注焦点的单个细胞。旨在确定胶质瘤特异性靶点的特定药物研发方法已产生了一些治疗选择,这些选择允许高度选择性地开发新试剂。结合新的分区给药方式,可能会减少全身并发症,并利用靶点的分区特异性,否则在全身应用的情况下,该靶点不会那么特异或会有副作用。从神经肿瘤学治疗发展的现状来看,可以预期会出现足够数量的药物靶点,这些靶点可通过间质或腔内给药来利用,它们无神经毒性,甚至可以通过新的代谢成像方式对其作用进行成像。对流增强给药、条件性复制的溶瘤病毒以及可移动的、基因工程改造的神经干细胞似乎都满足了有效治疗胶质瘤所需的分布要求,以克服手术、传统化疗和放疗所提供的非常有限的疗效。虽然基于基因组学的发现方法并非神经肿瘤学所特有,但给药策略的发展对中枢神经系统具有高度特异性,从而创造了一套独特的针对特定器官和疾病的治疗方法。