髓母细胞瘤（MB）是儿童最常见的恶性脑肿瘤，需要强化多模式治疗。长期生存率仍然令人不满意，最重要的是，幸存者经常患有严重的治疗相关疾病。 SHH MB 中的声波刺猬通路 (SHH) 为特定治疗药物提供了一个有希望的靶标。小分子 Vismodegib 以变构方式抑制 SMO（SHH 的主要上游激活剂）。在小鼠和临床研究中，Vismodegib 已被证明可有效治疗 MB。然而，由于全身应用于幼年小鼠和儿童后，骨骺生长板过早融合是不可逆的，其在儿科患者中的实施受到限制。脑室内 Vismodegib 应用可能为儿科髓母细胞瘤患者提供一种有前景的新型治疗策略。对患有髓母细胞瘤的婴儿 Math1-cre::Ptch1 Fl/Fl 小鼠进行脑室内 Vismodegib 治疗，以评估对肿瘤生长和全身副作用的疗效。对 Math1-cre::Ptch1 Fl/Fl 小鼠进行脑室内 Vismodegib 治疗后，仅两天后肿瘤就完全或部分缓解。脑室内治疗还以剂量依赖性方式显着改善无症状生存期。同时，心室内应用可以防止解剖或组织学骨畸形形式的全身副作用。我们得出的结论是，心室内应用 SHH 通路抑制剂结合了特定治疗药物的优点与精确的药物输送，并可能发展成为一种有前途的新疗法。 SHH MB 患者的靶向治疗方式。© 作者 2023。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

Medulloblastoma (MB) is the most common malignant brain tumor in children and requires intensive multimodal therapy. Long-term survival is still dissatisfying and, most importantly, survivors frequently suffer from severe treatment-associated morbidities. The sonic hedgehog pathway (SHH) in SHH MB provides a promising target for specific therapeutic agents. The small molecule Vismodegib allosterically inhibits SMO, the main upstream activator of SHH. Vismodegib has proven effective in the treatment of MB in mice and in clinical studies. However, due to irreversible premature epiphyseal growth plate fusions after systemic application to infant mice and children, its implementation to pediatric patients has been limited. Intraventricular Vismodegib application might provide a promising novel treatment strategy for pediatric medulloblastoma patients.Infant medulloblastoma-bearing Math1-cre::Ptch1 Fl/Fl mice were treated with intraventricular Vismodegib in order to evaluate efficacy on tumor growth and systemic side effects.We show that intraventricular Vismodegib treatment of Math1-cre::Ptch1 Fl/Fl mice leads to complete or partial tumor remission only two days after completed treatment. Intraventricular treatment also significantly improved symptom-free survival in a dose-dependent manner. At the same time, intraventricular application prevented systemic side effects in the form of anatomical or histological bone deformities.We conclude that intraventricular application of a SHH pathway inhibitor combines the advantages of a specific treatment agent with precise drug delivery and might evolve as a promising new way of targeted treatment for SHH MB patients.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.