Abstract
Meningiomas are the most common type of primary central nervous system tumors. Approximately, 80% of meningiomas are classified by the World Health Organization (WHO) as grade I, and 20% of these tumors are grade II and III, considered high-grade meningiomas (HGMs). Clinical control of HGMs, as well as meningiomas that relapse after surgery, and radiation therapy is difficult, and novel therapeutic approaches are necessary. However, traditional chemotherapies, interferons, hormonal therapies, and other targeted therapies have so far failed to provide clinical benefit. During the last several years, next generation sequencing has dissected the genetic heterogeneity of meningioma and enriched our knowledge about distinct oncogenic pathways driving different subtypes of meningiomas, opening up a door to new personalized targeted therapies. Molecular classification of meningioma allows a new design of clinical trials that assign patients to corresponding targeted agents based on the tumor genetic subtypes. In this review, we will shed light on emerging medical treatments of meningiomas with a particular focus on the new targets identified with genomic sequencing that have led to clinical trials testing novel compounds. Moreover, we present recent development of patient-derived preclinical models that provide platforms for assessing targeted therapies as well as strategies with novel mechanism of action such as oncolytic viruses.
Highlights
Meningiomas are tumors that arise from the membranes surrounding the brain and spinal cord, and they are the most common intracranial tumors
Besides NF2, 4 genes, SMO, TNF-receptor associated factor 7 (TRAF7), AKT, and KLF4 have been identified from a series of whole genome and exome sequencing efforts conducted on clinical meningioma specimens; these mutations are present in 40% of sporadic meningiomas and are mutually exclusive with chromosome 22 mutations including NF2 [5,21,22]
Despite advances in surgery and radiotherapy, rates of recurrence are high in World Health Organization (WHO) grade II
Summary
Meningiomas are tumors that arise from the membranes surrounding the brain and spinal cord, and they are the most common intracranial tumors. Heterogeneity is one of the main causes of failure of novel treatments; in most trials patients are enrolled based on their WHO grade and resistance to the standard of care as opposed to genetic driver mutations. In the last 5 years, generation sequencing has dissected the molecular heterogeneity and enriched our knowledge about the genetic drivers that could subdivide meningiomas based on molecular backgrounds. This has opened opportunities for new targets and novel treatments to test in the clinics based on the identified genetic mutations. We present the most recent preclinical platforms including patient-derived animal models developed to study meningioma biology and test treatments with novel mechanism of action such as oncolytic virus
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