Inhibiting kinases in malignant gliomas.

Advances in the understanding of glioma pathogenesis have led to increasing interest in the development of targeted molecular agents, and especially kinase inhibitors, for treatment of malignant gliomas. Protein kinases are a large family of enzymes that function as key regulators of cellular signaling pathways governing diverse functions, such as cell proliferation, growth, differentiation, invasion, angiogenesis and apoptosis in malignant gliomas. Preliminary clinical results with kinase inhibitors suggest that they are generally well-tolerated but have shown only modest activity. However, valuable information was obtained from these early clinical trials that will help the future development of these agents. This article reviews the important protein kinases in malignant gliomas, summarizes the existing clinical development of kinase inhibitors and discusses strategies to improve their effectiveness.