Potential of gene therapy for brain tumors.

Abstract

Brain tumors comprise a broad spectrum of biological and clinical entities making it unlikely for any single therapeutic approach to be universally applicable. In particular, malignant glioblastoma multiforme have defied all current therapeutic modalities. Gene therapy offers the potential to augment current neurosurgical, radiation and drug treatments with little increase in morbidity. Many therapeutic transgenes have shown efficacy in experimental models, including generation of toxic compounds, enzymatic activation of pro-drugs, expression of tumor suppressor or apoptotic proteins, inhibition of angiogenesis and enhancement of immune responses to tumor antigens. Vectors have been used as gene delivery vehicles and as cytotoxic agents in their own right by selective replication and lysis of tumor cells, thereby also generating vectors on-site. Brain tumors appear to offer some "Achilles' heels" in that they are usually contained within the brain and represent a unique dividing cell population there. However, the heterogeneous and invasive characteristics of these tumor cells, as well as sequestration of tumor antigens within a relatively immune privileged location present serious problems for effective therapy. This review will focus on current transgene/vector strategies, including novel therapeutic genes, combinational therapies and new delivery modalities, the latter of which appears to be the rate limiting factor for gene therapy of brain tumors in humans.