Advances in molecular therapies in patients with brain tumors.

Abstract

We are witnessing the development of new treatment modalities for primary brain tumors. An area under intense investigation is the use of small molecules targeting intracellular signaling pathways that interfere with growth, invasion, and metastasis of high-grade gliomas. We review clinical trials of small molecules in adults with brain tumors. This search included electronic databases, specialty journals, textbooks, proceedings, and Web sites of the National Cancer Institute and other cooperative brain tumor groups in Europe and the United States. Several drugs with the ability to down-regulate the growth and invasion of malignant gliomas are at various stages of testing. Most of these focus on interfering with oncogenic and tumor survival pathways. Examples include inhibitors of tyrosine kinases, farnesyltransferases, and matrix metalloproteinases. These molecules are at different stages of testing, and a conclusive picture of which drug is most effective, either alone or in combination, needs better definition. The metalloproteinase inhibitor marimastat with temozolomide has given the best results to date in phase II trials, increasing the rate of 6-month progression-free survival for recurrent glioblastoma multiforme and anaplastic gliomas. As our understanding of the biology of gliomas increases and new drugs targeting specific molecular pathways enter well-designed cooperative trials, the control and prognosis of these tumors should improve.