Project 171061

While significant advances have recently been made in the treatment of a variety of cancers, brain tumours called gliomas have generally remained resistant to current drugs. As such, there currently exists a desperate need for the rapid development and evaluation of new agents for the eradication of these devastating tumours. Improving the efficiency of the early development of novel agents for the treatment of gliomas requires the identification of novel biological targets as well as adoption of novel strategic approaches. We have been evaluating, in rodents, the use of a number of therapeutic agents, with novel mechanisms of action, for the treatment of gliomas. Preliminary data from one of these agents, namely YC-1, indicates it to be an attractive candidate for further investigations. In this proposal, we plan to use multiple, novel means of evaluation of therapeutic potential to provide a comprehensive analysis of the efficacy of new anti-glioma agents, such as YC-1. Imaging of mouse and rat models of glioma offers an elegant means of assessing the efficacy of novel therapeutic agents. The full potential of imaging in the evaluation of anti-cancer agents, however, has yet to be realized. The majority of imaging studies evaluating therapeutic efficacy have focused on relatively simple measures, such as magnetic resonance imaging (MRI)-defined change in tumor volume. The advent of sophisticated quantitative imaging techniques, which allow for visualization of intrinsic structural, functional, and molecular properties of gliomas, promises a more powerful means of monitoring the diverse effects of modern experimental therapeutic agents on the natural evolution of these tumours. As such, we plan to combine advanced MRI, positron emission tomography (PET), and quantitative immunohistochemistry (qIHC) measurements to provide a complete evaluation of the potential for advancing promising agents to studies involving human patients suffering from glioma.

using multi-parametric imaging (MRI, PET) and quantitative immunohistochemistry to evaluate novel therapeutic agents in rodent models of glioma