Drug Resistance in Malignant Meningiomas

Abstract

Meningiomas are one of the most common intracranial tumors and arise from the arachnoid cap cell. Although the overwhelming majority of meningiomas are benign, approximately 5-15 % of meningiomas are non-benign. These tumors are histologically Grade II and III and have a propensity to be aggressive and occasionally metastasize. Multiple genetic abnormalities and epigenetic changes are involved in the formation and malignant transformation of meningioma. Given the aggressiveness of these tumors, the standard of care involves maximal surgical resection, when feasible and safe, followed by radiation. In cases of initial treatment failure or tumor recurrence, adjuvant therapy with chemotherapy or clinical trials becomes an option. Outcomes data for chemotherapy are rather scarce, but medical treatment options include mifepristone, hydroxyurea, somatostatin analogues, interferon-a, irinotecan, and temozolomide. Somatostatin analogues and interferon-a have shown promise, but prospective studies will be necessary to determine their effect on outcomes. Future development of medical treatments and chemotherapy depends upon the understanding of mitogenic and antiapoptotic pathways involved with malignant meningiomas. Multiple growth factors and receptors may serve as useful sites for therapy action. Multiple preclinical and clinical trials are underway for the disruption of these pathways. Future prospective, randomized clinical trials will be essential to evaluate the effect on tumor control, progression-free survival, and effect on overall survival.