Building a new arsenal: repurposed drugs and metronomic chemotherapy against medulloblastoma.
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INTRODUCTION: Medulloblastoma (MB) represents the most prevalent malignant pediatric brain tumor. Although survival has greatly improved, the tumor and its treatments have devastating long-term side effects that negatively impact quality of survival. Consequently, there is a critical need for innovative therapeutic strategies aimed at enhancing patient outcomes and mitigating treatment-related toxicities. AREAS COVERED: In this review, the authors summarize the current evidence regarding metronomic chemotherapy (MC) and drug repurposing in MB and discuss prospective future developments by searching the PubMed database from 1980 to 2025. Drug repurposing (DR), defined as the identification of novel therapeutic applications for existing pharmacological agents, presents a promising strategy to expedite the development of effective and well-tolerated treatments. Metronomic chemotherapy, characterized by the frequent administration of low-dose chemotherapeutic agents, exerts its therapeutic effects by targeting the tumor microenvironment and angiogenesis. Notably, metronomic chemotherapy, particularly in multidrug combinations incorporating repurposed agents, has demonstrated significant clinical activity in patients with relapsing/refractory MB. EXPERT OPINION: Data on MC and DR, published over the past decades, has confirmed their potential to prolong survival and potentially cure patients with refractory/relapsing MB. Randomized trials are now mandatory to generate higher levels of evidence.