Medulloblastoma (MB) is the most common childhood malignant brain tumor, accounting for approximately 20% of all pediatric central nervous system tumors. Current standard treatments involving surgical interventions followed by craniospinal irradiation and adjuvant chemotherapy have severe motor and cognitive defects. Therefore, individualized treatment regimens with reduced toxicity designed according to the presence of specific oncogenic 'driver' genes are urgently demanded. To this end, recent genetic and epigenetic findings have advanced the classification of MB into the international consensus of four distinct MB molecular subgroups (WNT, SHH, Group 3, and Group 4) based on their respective molecular and histopathological characteristics. More recent studies have indicated that up to seven molecular subgroups exist in childhood MB. Moreover, studies on the inter- and intra-tumoral features of the four subgroups revealed that each subgroup contains variant subtypes. These results have greatly helped risk stratification of MB patients at diagnosis and significantly improved clinical treatment options. Herein, we highlight the recent advances and challenges associated with MB classification, and the development of therapeutic treatments targeting novel subgroup-specific molecular and epigenetic factors, especially those in the SHH-driven MB tumors.

中文翻译：

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髓母细胞瘤：分子理解，治疗进展和新进展。

髓母细胞瘤（MB）是儿童期最常见的恶性脑肿瘤，约占所有儿科中枢神经系统肿瘤的20％。当前的标准治疗方法包括外科手术，颅脑脊髓照射和辅助化学疗法，均存在严重的运动和认知缺陷。因此，迫切需要根据特定致癌“驱动”基因的存在设计的降低毒性的个体化治疗方案。为此，最近的遗传学和表观遗传学发现已将MB的分类基于其各自的分子和组织病理学特征，推进到四个不同的MB分子亚组（WNT，SHH，Group 3和Group 4）的国际共识。最近的研究表明，儿童MB中存在多达七个分子亚组。此外，对四个亚组的肿瘤间和肿瘤内特征的研究表明，每个亚组都包含变异亚型。这些结果极大地帮助了MB患者诊断时的风险分层，并显着改善了临床治疗选择。在本文中，我们重点介绍了与MB分类相关的最新进展和挑战，以及针对新型亚组特异性分子和表观遗传因素（尤其是SHH驱动的MB肿瘤中的那些）的治疗方法的开发。