High-grade glioma mouse models and their applicability for preclinical testing
Received 9 June 2009; received in revised form 15 August 2009; accepted 24 August 2009. published online 22 September 2009.
Summary
High-grade gliomas (WHO grade III anaplastic astrocytoma and grade IV glioblastoma multiforme) are the most common primary tumors in the central nervous system in adults. Unfortunately, despite great efforts in finding better therapies, high-grade glioma remains among the most devastating and deadliest of all human cancers. During recent years, genetic and molecular alterations that underlie this disease have been identified and advanced our basic knowledge about gliomagenesis. Moreover, understanding the molecular biology has also led to the development of genetically engineered mouse models that resemble many of the features of human gliomas. Ideally, such “patient-like” models should be instrumental for preclinical testing of novel therapeutics, but thus far they have not yet been widely implemented for this purpose. This review will discuss the advantages and shortcomings of the established high-grade glioma mouse models with emphasis on their potential applicability for preclinical testing of novel drugs and treatment regimens.
aDepartment of Clinical Chemistry, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Hospital), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
bDepartment of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital), Louwesweg 6, 1066 EC Amsterdam, The Netherlands
cDivision of Drug Toxicology, Faculty of Pharmacy, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands