髓母细胞瘤 (MB) 是儿童中最常见的恶性实体瘤。 MB 的常规治疗方案包括手术切除肿瘤，然后进行放疗和化疗。然而，这种方法与显着的发病率和有害的副作用相关。因此，迫切需要更精确、危害更小的治疗方法，以提高幸存者的生活质量。 CEP-18770 是一种针对 20S 亚基的新型蛋白酶体抑制剂，由于其在转移性实体瘤和多发性骨髓瘤中的抗癌活性以及可接受的安全性，已成为一种有前途的候选药物。在这项研究中，我们旨在通过采用多种 MB 患者来源的细胞和细胞系来评估 CEP-18770 的抗癌功效。我们的临床前研究表明，CEP-18770 可有效抑制 MBs 细胞中的蛋白酶体活性并诱导细胞凋亡。此外，我们发现 CEP-18770 和顺铂（MB 疗法的当前成分）表现出​​协同凋亡作用。本文表明，CEP-18770 具有作为 MB 肿瘤辅助治疗的潜力，从而为更具针对性和毒性较小的治疗策略铺平了道路。

Medulloblastomas (MBs) represent the most prevalent malignant solid tumors in kids. The conventional treatment regimen for MBs includes surgical removal of the tumor, followed by radiation and chemotherapy. However, this approach is associated with significant morbidity and detrimental side effects. Consequently, there is a critical demand for more precise and less harmful treatments to enhance the quality of life for survivors. CEP-18770, a novel proteasome inhibitor that targets the 20S subunit, has emerged as a promising candidate, due to its anticancer activity in metastatic solid tumors and multiple myeloma, coupled with an acceptable safety profile. In this study, we aimed to assess the anticancer efficacy of CEP-18770 by employing a variety of MB patient-derived cells and cell lines. Our preclinical investigations revealed that CEP-18770 effectively inhibits proteasome activity and induces apoptosis in MBs cells. Furthermore, we discovered that CEP-18770 and cisplatin, a current component of MB therapy, exhibit a synergistic apoptotic effect. This paper shows that CEP-18770 holds potential as an adjunctive treatment for MB tumors, thereby paving the way for more targeted and less toxic therapeutic strategies.