The role of MEK inhibition in pediatric low-grade gliomas

Shehryar R Sheikh; Laura J Klesse; Ross Mangum; Ashley Bui; Benjamin I Siegel; Mohamed S Abdelbaki; Neha J Patel

doi:10.3389/fonc.2024.1503894

The role of MEK inhibition in pediatric low-grade gliomas

Front Oncol. 2024 Dec 20:14:1503894. doi: 10.3389/fonc.2024.1503894. eCollection 2024.

Authors

Shehryar R Sheikh^{1

2}, Laura J Klesse^#³, Ross Mangum^#⁴, Ashley Bui^#³, Benjamin I Siegel^#^{5

6}, Mohamed S Abdelbaki^#⁷, Neha J Patel^#⁸

Affiliations

¹ Department of Neurosurgery, Cleveland Clinic, Cleveland, OH, United States.
² Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH, United States.
³ Department of Pediatrics, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas, TX, United States.
⁴ Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, United States.
⁵ Brain Tumor Institute, Children's National Hospital, Washington, DC, United States.
⁶ Division of Neurology, Children's National Hospital, Washington, DC, United States.
⁷ Division of Hematology and Oncology, Department of Pediatrics, School of Medicine, Washington University, St. Louis, MO, United States.
⁸ Department of Pediatric Hematology-Oncology and Blood and Marrow Transplant, Cleveland Clinic, Cleveland, OH, United States.

^# Contributed equally.

Abstract

Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Many patients with unresectable tumors experience recurrence or long-term sequelae from standard chemotherapeutics. This mini-review explores the emerging role of MEK inhibitors in the management of pLGGs, highlighting their potential to transform current treatment paradigms. We review the molecular basis for therapeutic MEK inhibition in the context of pLGG, provide an evidence base for the use of the major MEK inhibitors currently available in the market for pLGG, and review the challenges in the use of MEKi inhibitors in this population.

Keywords: MAPK; MEK; MEKi; PLGG; pediatric low grade glioma; targeted therapy.

Publication types

Review

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.