New molecular targets in meningiomas: The present and the future

Vyshak Alva Venur, Sandro Santagata, Eva Galanis, Priscilla K. Brastianos

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

Abstract

Purpose of review Meningiomas, the most common primary brain tumor, have historically been managed with surgery and radiation. Traditional chemotherapy has not been effective. Fortunately, recent advances in genetic sequencing have led to an improved understanding of the molecular drivers in meningioma. This article aims to discuss the diagnostic and therapeutic implications of recently discovered genetic alterations in meningiomas. Recent findings Many of the recently discovered genetic alterations correlate with distinct clinical phenotypes. SMO, AKT and PIK3CA mutations are enriched in the anterior skull base. KLF4 mutations are specific for secretory histology, and BAP1 alterations are common in progressive rhabdoid meningiomas. Alterations in TERT, DMD and BAP1 correlate with poor clinical outcomes. Importantly, the discovery of clinically actionable alterations in a number of genes, including SMO, AKT1 and PIK3CA, has opened up novel potential avenues for therapeutic management of meningiomas. Overexpression of PD-L1 in higher grade meningiomas also provides preclinical support for the investigation of checkpoint blockade. Summary The discovery of genetic alterations has improved our understanding of the natural history and classification of meningiomas. Clinical trials with several novel agents targeting driver mutations are currently accruing patients and they can lead to better treatment strategies.

Original languageEnglish (US)
Pages (from-to)740-746
Number of pages7
JournalCurrent opinion in neurology
Volume31
Issue number6
DOIs
StatePublished - 2018

Keywords

  • AKT
  • BAP1
  • DMD
  • KLF4
  • PD-L1
  • SMO
  • checkpoint blockade
  • meningioma
  • targeted therapies

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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