Receptor tyrosine kinase signaling in gliomagenesis - Pathobiology and therapeutic approaches

Gliomas are a large collection of primary central nervous system tumors that arise from glia, astrocytes and oligodendrocytes or their precursors. They are graded on a scale of I to IV based on their degree of malignancy as judged by variable histological features. Genetic and biochemical evidences 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 PI3-kinase/ Akt and Ras/Raf/MEK/MAPK pathways, which provides a number of novel targets for glioma therapy. This article aims to present a broad understanding of the receptor tyrosine kinase 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 for this refractory disease.