Epigenomics and immunotherapeutic advances in pediatric brain tumors

Abstract

Brain tumors are the leading cause of childhood cancer-related deaths. Similar to adult brain tumors, pediatric brain tumors are classified based on histopathological evaluations. However, pediatric brain tumors are often histologically inconsistent with adult brain tumors. Recent research findings from molecular genetic analyses have revealed molecular and genetic changes in pediatric tumors that are necessary for appropriate classification to avoid misdiagnosis, the development of treatment modalities, and the clinical management of tumors. As many of the molecular-based therapies developed from clinical trials on adults are not always effective against pediatric brain tumors, recent advances have improved our understanding of the molecular profiles of pediatric brain tumors and have led to novel epigenetic and immunotherapeutic treatment approaches currently being evaluated in clinical trials. In this review, we focus on primary malignant brain tumors in children and genetic, epigenetic, and molecular characteristics that differentiate them from brain tumors in adults. The comparison of pediatric and adult brain tumors highlights the need for treatments designed specifically for pediatric brain tumors. We also discuss the advancements in novel molecularly targeted drugs and how they are being integrated with standard therapy to improve the classification and outcomes of pediatric brain tumors in the future.

Childhood Malignant Brain Tumors: Balancing the Bench and Bedside

“…The paradigm shift in understanding of the molecular heterogeneity of pHGG, together with the failure of conventional therapeutics to significantly improve outcomes for several years, has shifted focus towards developing novel agents that manipulate the epigenetic and genomic aberrations inherent in pHGG molecular subgroups, immunotherapies, and the development of alternative drug administration routes to penetrate the blood–brain barrier such as convection enhanced delivery for diffuse midline glioma H3K27 mutant/DIPG [ 92 , 101 , 102 , 103 , 104 , 105 ].…”

Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours

“…Multiple histone mutations and epigenetic aberrations have been found in this subtype. Some targeted therapies in early clinical trials for the SHH group and decreases in the chemo and radio doses are being implemented to achieve the same efficacy as that achieved for the WNT group, but there are no specific treatments developed for groups 3 and 4 [5,36].…”

“…MB presents great heterogeneity, even within each subgroup. These subgroups differ in many features, such as cells of origin, tumour vasculature/architecture, molecular mutations, alterations in epigenetic regulators, and prognosis [ 5 , 36 , 40 ].…”

“…Paediatric CNS tumours have not been as extensively studied as the adult ones. They differ in many aspects, such as clinical presentation, histological distribution, gene mutations, embryological origins, location, and the tumour microenvironment (TME), making them respond differently to the treatments [ 5 , 6 ]. Moreover, we must consider that the paediatric immune system is developing and age-dependent, leading to differences in treatment response [ 7 ].…”

“…Advances in molecular characterisation in the last years have brought the identification of new potential targeted molecular therapies that are being tested in early-phase clinical trials [ 5 , 8 ].…”