Perspectives of cellular and molecular neurosurgery.
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.
Westphal
Manfred
M
Department of Neurosurgery, University Hospital Hamburg Eppendorf, Hamburg, Germany. westphal@uke.uni-hamburg.de
Black
Peter McL
PM
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000628:therapy*; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000628:therapy*; D006801:Humans; D019635:Neurosurgical Procedures
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor