Brain cancers are a leading cause of mortality in children. Brainstem glioma constitutes 10% of all pediatric central nervous system tumors, the most common type being a high grade diffuse midline glioma (DMG). Preclinical discoveries fail to translate into clinical success due to: i) drug systemic toxicity, and ii) lack of drug penetration into the brain/tumor. This Innosuisse funded project aims to engineer novel drugs with increased clinical efficacy. To this end, we will design, synthesize and validate anticancer therapeutics that specifically penetrate the blood-brain barrier (BBB). This precision medicine approach will not only increase BBB penetration, but also provide targeted drug delivery, thereby reducing systemic toxicity. Our goal is to develop novel treatment options for childhood brain tumors for which there is currently no cure.