Abstract
INTRODUCTION: Despite substantial improvements in standards of care, the most common aggressive pediatric and adult high-grade gliomas (HGG) carry uniformly fatal diagnoses due to unique treatment limitations, high recurrence rates and the absence of effective treatments following recurrence. Recent advancements in our understanding of the pathophysiology, genetics and epigenetics as well as mechanisms of immune surveillance during gliomagenesis have created new knowledge to design more effective and target-directed therapies to improve patient outcomes. AREAS COVERED: In this review, the authors discuss the critical genetic, epigenetic and immunologic aberrations found in gliomas that appear rational and promising for therapeutic developments in the presence and future. The current state of the latest therapeutic developments including tumor-specific targeted drug therapies, metabolic targeting, epigenetic modulation and immunotherapy are summarized and suggestions for future directions are offered. Furthermore, they highlight contemporary issues related to the clinical development, such as challenges in clinical trials and toxicities. EXPERT OPINION: The commitment to understanding the process of gliomagenesis has created a catalogue of aberrations that depict multiple mechanisms underlying this disease, many of which are suitable to therapeutic inhibition and are currently tested in clinical trials. Thus, future treatment endeavors will employ multiple treatment modalities that target disparate tumor characteristics personalized to the patient's individual tumor.