Advances in Molecular Biological and Translational Studies in World Health Organization Grades 2 and 3 Meningiomas: A Literature Review

Abstract

The treatment of World Health Organization (WHO) grades 2 and 3 meningiomas remains difficult and controversial. The pathogenesis of high-grade meningiomas was expected to be elucidated to improve treatment strategies. The molecular biology of meningiomas has been clarified in recent years. High-grade meningiomas have been linked to NF2 mutations and 22q deletion. CDKN2A/B homozygous deletion and TERT promoter mutations are independent prognostic factors for WHO grade 3 meningiomas. In addition to 22q loss, 1p, 14p, and 9q loss have been linked to high-grade meningiomas. Meningiomas enriched in copy number alterations may be biologically invasive. Furthermore, several new comprehensive classifications of meningiomas have been proposed based on these molecular biological features, including DNA methylation status. The new classifications may have implications for treatment strategies for refractory aggressive meningiomas because they provide a more accurate prognosis compared to the conventional WHO classification. Although several systemic therapies, including molecular targeted therapies, may be effective in treating refractory aggressive meningiomas, these drugs are being tested. Systemic drug therapy for meningioma is expected to be developed in the future. Thus, this review aims to discuss the distinct genomic alterations observed in WHO grade 2 and 3 meningiomas, as well as their diagnostic and therapeutic implications and systemic drug therapies for high-grade meningiomas.

The Novel MDM4 Inhibitor CEP-1347 Activates the p53 Pathway and Blocks Malignant Meningioma Growth In Vitro and In Vivo

“…The management of aggressive meningiomas that resist standard treatment with surgery and radiotherapy, as exemplified by malignant meningiomas, is in desperate need of novel treatment strategies. A number of agents are currently being developed for this purpose, but all are still in the experimental stages, which warrants further approaches that target the hitherto unknown vulnerabilities of aggressive meningiomas [7][8][9][10][11][12]. We herein investigated the potential of the CEP-1347-mediated activation of wild-type p53 as a novel therapeutic approach in the management of malignant meningiomas.…”

“…With recent advances in our understanding of genetic/epigenetic and molecular changes associated with the development and/or progression of meningioma, drugs targeting these changes are attracting increasing attention and are now being exhaustively tested for their anti-meningioma activity in preclinical and clinical studies [7][8][9][10][11][12]. Although some drugs, such as bevacizumab and everolimus, have so far shown promising results, none have yet to exhibit unequivocal clinical efficacy [7][8][9][10][11][12], underscoring the necessity of continued efforts to pursue therapeutic targets from novel perspectives.…”