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.
中枢神经系统肿瘤是儿童癌症相关死亡的首要原因，其中部分恶性肿瘤的预后仍然不容乐观。尽管过去二十年间外科手术、放射治疗及靶向治疗领域已取得进展，但若干未解决的重大障碍仍持续影响治疗效果。这些挑战包括血脑屏障导致的药物递送效率不足、显著的肿瘤内分子异质性以及复杂的肿瘤微环境。药物再利用——即通过新型颅内给药方法重新应用已获美国食品药品监督管理局批准且具有中枢神经系统渗透证据的药物，以实现最佳药物暴露——已成为当前研究热点。这一策略具有重要价值，因为大多数此类药物已完成漫长的研发流程，其安全风险与药代动力学特征已得到充分评估，现可通过加速且差异化的路径进行临床验证。结论：下一代治疗策略应优先考虑重新利用已获批用于其他适应症的肿瘤及非肿瘤药物，特别是那些在儿童脑肿瘤临床前研究中展现出显著活性的药物。结合新型给药技术，这类药物有望为儿童神经肿瘤治疗带来重要突破。
Advances in the Repurposing and Blood–Brain Barrier Penetrance of Drugs in Pediatric Brain Tumors
肿瘤(癌症)患者之家