Systemic treatment of central nervous system tumors

Abstract

Brain and nervous system tumors account for 1.6% of all new cancer cases, approximately 30 % are malignant. The most common type is represented by gliomas; Glioblastoma is the most aggressive brain tumor. For newly diagnosed high-grade glioma, the standard of care consists of resection, followed by radiotherapy and adjuvant temozolomide. Even with aggressivemultimodal treatment, high grade glioma has poor prognosis and high relapse rate. At the time of disease recurrence, we have few treatment options. Chemotherapy has modestly effective as systemic agent. One of the major causes is the presence of blood brain barrier compromising the entry of several drugs in brain. Alkylating agents, platinum salts, etoposide and antimetabolite are the most efficient chemotherapeutic drugs. High grade glioma are highly vascular tumors, bevacizumab is an anti-vascular endothelial growth factor effective in recurrent high grade glioma. Several molecular alterations have been described in high grade glioma, that have diagnostic, prognostic, and predictive value. 1p19q codeletion, Methylation of MGMT and IDH mutation are predictive to response to chemotherapy. An improved understanding of this molecular pathways, Overexpression, activation, and dysregulation of various membrane receptors, has led to the evaluation of several agents targeting tumor cells and the tumor microenvironment.