Rechberger Julian S, Toll Stephanie A, Biswas Subhasree, You Hyo Bin, Chow William D, Kendall Nicholas, Navalkele Pournima, Khatua Soumen
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Children's Hospital of Michigan, Central Michigan University School of Medicine, Saginaw, MI 48602, USA.
Cancers (Basel). 2025 Jan 27;17(3):439. doi: 10.3390/cancers17030439.
Central nervous system (CNS) tumors are the leading cause of cancer-related mortality in children, with prognosis remaining dismal for some of these malignancies. Though the past two decades have seen advancements in surgery, radiation, and targeted therapy, major unresolved hurdles continue to undermine the therapeutic efficacy. These include challenges in suboptimal drug delivery through the blood-brain barrier (BBB), marked intra-tumoral molecular heterogeneity, and the elusive tumor microenvironment. Drug repurposing or re-tasking FDA-approved drugs with evidence of penetration into the CNS, using newer methods of intracranial drug delivery facilitating optimal drug exposure, has been an area of intense research. This could be a valuable tool, as most of these agents have already gone through the lengthy process of drug development and the evaluation of safety risks and the optimal pharmacokinetic profile. They can now be used and tested in clinics with an accelerated and different approach. Conclusions: The next-generation therapeutic strategy should prioritize repurposing oncologic and non-oncologic drugs that have been used for other indication, and have demonstrated robust preclinical activity against pediatric brain tumors. In combination with novel drug delivery techniques, these drugs could hold significant therapeutic promise in pediatric neurooncology.
中枢神经系统（CNS）肿瘤是儿童癌症相关死亡的主要原因，其中一些恶性肿瘤的预后仍然很差。尽管在过去二十年里，手术、放疗和靶向治疗取得了进展，但尚未解决的主要障碍继续削弱治疗效果。这些障碍包括通过血脑屏障（BBB）进行次优药物递送的挑战、显著的肿瘤内分子异质性以及难以捉摸的肿瘤微环境。利用促进最佳药物暴露的新型颅内药物递送方法，对已证明能穿透中枢神经系统的FDA批准药物进行药物重新利用或重新定位，一直是一个深入研究的领域。这可能是一个有价值的工具，因为这些药物中的大多数已经经历了漫长的药物开发过程以及安全风险评估和最佳药代动力学特征评估。现在可以采用加速且不同的方法在临床上使用和测试它们。结论：下一代治疗策略应优先考虑重新利用已用于其他适应症且已证明对小儿脑肿瘤具有强大临床前活性的肿瘤学和非肿瘤学药物。与新型药物递送技术相结合，这些药物在小儿神经肿瘤学中可能具有重大的治疗前景。
