Therapeutic Targets in Diffuse Midline Gliomas—An Emerging Landscape

SIMPLE SUMMARY: Diffuse midline gliomas (DMGs) remain one of the most devastating childhood brain tumour types, for which there is currently no known cure. In this review we provide a summary of the existing knowledge of the molecular mechanisms underlying the pathogenesis of this disease, highlighting current analyses and novel treatment propositions. Together, the accumulation of these data will aid in the understanding and development of more effective therapeutic options for the treatment of DMGs. ABSTRACT: Diffuse midline gliomas (DMGs) are invariably fatal pediatric brain tumours that are inherently resistant to conventional therapy. In recent years our understanding of the underlying molecular mechanisms of DMG tumorigenicity has resulted in the identification of novel targets and the development of a range of potential therapies, with multiple agents now being progressed to clinical translation to test their therapeutic efficacy. Here, we provide an overview of the current therapies aimed at epigenetic and mutational drivers, cellular pathway aberrations and tumor microenvironment mechanisms in DMGs in order to aid therapy development and facilitate a holistic approach to patient treatment.