Chapter 4 - Brain Tumor Models for Cancer Therapy

Abstract

This chapter discusses the various types of animal models used for studying cancer therapy of brain tumors. The most frequently used preclinical in vivo models of brain tumors include the rat carcinogen-induced syngeneic models and human tumor xenografts. Both types of tumors are routinely implanted subcutaneously or intracranially in host animals including conventional and nude rats or nude or SCID mice. These models have been used to explore the efficacy of diverse therapeutic strategies. Rat brain tumor models have been widely used in experimental neuro-oncology studies for more than 30 years. The 9L gliosarcoma of the Fischer 344 rat is a carcinogen-induced cell line that results from nitrosourea exposure. The blood–brain barrier remains a very active area of investigation even though the blood–brain tumor barrier is more permeable than the blood–brain barrier. Although liposomes have been used as a vehicle for delivery of therapeutic agents in oncology, the penetration of liposomes through the blood–brain barrier is very poor. The most widely explored gene therapy paradigm is based on the activation of ganciclovir to a cytotoxic compound by a viral enzyme, thymidine kinase, which is expressed by tumor cells, after infection by a retroviral vector containing the gene. Several new drugs such as S16020 have been assessed in preclinical brain tumor models.