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Novel delivery strategies for glioblastoma.

ABSTRACT: Brain tumors--particularly glioblastoma multiforme--pose an important public health problem in the United States. Despite surgical and medical advances, the prognosis for patients with malignant gliomas remains grim: current therapy is insufficient with nearly universal recurrence. A major reason for this failure is the difficulty of delivering therapeutic agents to the brain: better delivery approaches are needed to improve treatment. In this article, we summarize recent progress in drug delivery to the brain, with an emphasis on convection-enhanced delivery of nanocarriers. We examine the potential of new delivery methods to permit novel drug- and gene-based therapies that target brain cancer stem cells and discuss the use of nanomaterials for imaging of tumors and drug delivery.

SUBMITTER: Zhou J

PROVIDER: S-EPMC3269656 | biostudies-literature | 2012 Jan-Feb

REPOSITORIES: biostudies-literature

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Novel delivery strategies for glioblastoma.

Zhou Jiangbing J Atsina Kofi-Buaku KB Himes Benjamin T BT Strohbehn Garth W GW Saltzman W Mark WM

Cancer journal (Sudbury, Mass.) 20120101 1

Brain tumors--particularly glioblastoma multiforme--pose an important public health problem in the United States. Despite surgical and medical advances, the prognosis for patients with malignant gliomas remains grim: current therapy is insufficient with nearly universal recurrence. A major reason for this failure is the difficulty of delivering therapeutic agents to the brain: better delivery approaches are needed to improve treatment. In this article, we summarize recent progress in drug delive ...[more]

PMID: 22290262

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Project description:Comprising more than half of all brain tumors, glioblastoma multiforme (GBM) is a leading cause of brain cancer-related deaths worldwide. A major clinical challenge is presented by the capacity of glioma cells to rapidly infiltrate healthy brain parenchyma, allowing the cancer to escape control by localized surgical resections and radiotherapies, and promoting recurrence in other brain regions. We propose that therapies which target cellular motility pathways could be used to slow tumor dispersal, providing a longer time window for administration of frontline treatments needed to directly eradicate the primary tumors. An array of signal transduction pathways are known to be involved in controlling cellular motility. Aquaporins (AQPs) and voltage-gated ion channels are prime candidates as pharmacological targets to restrain cell migration in glioblastoma. Published work has demonstrated AQPs 1, 4 and 9, as well as voltage-gated potassium, sodium and calcium channels, chloride channels, and acid-sensing ion channels are expressed in GBM and can influence processes of cell volume change, extracellular matrix degradation, cytoskeletal reorganization, lamellipodial and filopodial extension, and turnover of cell-cell adhesions and focal assembly sites. The current gap in knowledge is the identification of optimal combinations of targets, inhibitory agents, and drug delivery systems that will allow effective intervention with minimal side effects in the complex environment of the brain, without disrupting finely tuned activities of neuro-glial networks. Based on published literature, we propose that co-treatments using AQP inhibitors in addition to other therapies could increase effectiveness, overcoming some limitations inherent in current strategies that are focused on single mechanisms. An emerging interest in nanobodies as drug delivery systems could be instrumental for achieving the selective delivery of combinations of agents aimed at multiple key targets, which could enhance success in vivo.

Dataset Information

Novel delivery strategies for glioblastoma.

Publications

Novel delivery strategies for glioblastoma.

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