Signaling Modules in Glial Tumors and Implications for Molecular Therapy

Abstract

Gliomas (ependymomas are also considered gliomas) are the most common primary central nervous system tumors. They are graded on a scale of I-IV, based on their degree of malignancy as judged by variable histological features. Genetic and biochemical evidence have proven that gliomagenesis involves a stepwise accumulation of genetic lesions affecting either signal transduction pathways activated by receptor tyrosine kinases (RTKs) or cell cycle growth arrest pathways. Many of these observed molecular alterations are now being used to compliment clinical diagnosis. Genetic alterations affecting RTK signaling results in the activation of several downstream pathways, such as the phosphatidylinositol 3-kinase (PI3-K)/Akt and Ras/Raf/MEK/MAPK pathways, which provide a number of novel targets for glioma therapy. This chapter aims to present a broad understanding of the RTK signaling networks involved in gliomagenesis. Molecular classification of primary glial tumors and elucidation of cooperative interactions between different genetic lesions will eventually allow us to target distinct glioma subsets and will provide a more rational approach to adjuvant therapies.