Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, MD 21201, USA.
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Curr Pharm Des. 2024;30(1):31-47. doi: 10.2174/0113816128277350231219062154.
Medulloblastomas (MDB) are malignant, aggressive brain tumors that primarily affect children. The survival rate for children under 14 is approximately 72%, while for ages 15 to 39, it is around 78%. A growing body of evidence suggests that dysregulation of signaling mechanisms and noncoding RNA epigenetics play a pivotal role in this disease.
This study conducted an electronic search of articles on websites like PubMed and Google. The current review also used an databases search and bioinformatics analysis and an extensive comprehensive literature search for original research articles and review articles as well as retrieval of current and future medications in clinical trials.
This study indicates that several signaling pathways, such as sonic hedgehog, WNT/β-catenin, unfolded protein response mediated ER stress, notch, neurotrophins and TGF-β and ERK, MAPK, and ERK play a crucial role in the pathogenesis of MDB. Gene and ncRNA/protein are also involved as an axis long ncRNA to sponge micro-RNAs that affect downstream signal proteins expression and translation affection disease pathophysiology, prognosis and present potential target hit for drug repurposing. Current treatment options include surgery, radiation, and chemotherapy; unfortunately, the disease often relapses, and the survival rate is less than 5%. Therefore, there is a need to develop more effective treatments to combat recurrence and improve survival rates.
This review describes various MDB disease hallmarks, including the signaling mechanisms involved in pathophysiology, related-causal genes, epigenetics, downstream genes/epigenes, and possibly the causal disease genes/non-protein coding (nc)RNA/protein axis. Additionally, the challenges associated with MDB treatment are discussed, along with how they are being addressed using nano-technology and nano-biomedicine, with a listing of possible treatment options and future potential treatment modalities.
成神经管细胞瘤(MDB)是一种主要影响儿童的恶性、侵袭性脑肿瘤。14 岁以下儿童的存活率约为 72%,而 15 岁至 39 岁的存活率约为 78%。越来越多的证据表明,信号转导机制和非编码 RNA 表观遗传学的失调在这种疾病中起着关键作用。
本研究在 PubMed 和 Google 等网站上进行了文章的电子检索。本综述还使用了数据库搜索和生物信息学分析,以及对原始研究文章和综述文章的广泛综合文献搜索,以及检索临床试验中当前和未来的药物。
本研究表明,几种信号通路,如 sonic hedgehog、WNT/β-catenin、未折叠蛋白反应介导的 ER 应激、notch、神经营养因子和 TGF-β和 ERK、MAPK 和 ERK,在 MDB 的发病机制中起着至关重要的作用。基因和 ncRNA/蛋白质也作为一个轴 long ncRNA 参与,以海绵 micro-RNAs,影响下游信号蛋白的表达和翻译,影响疾病的病理生理学、预后,并为药物再利用提供潜在的靶标。目前的治疗选择包括手术、放疗和化疗;不幸的是,这种疾病经常复发,存活率不到 5%。因此,需要开发更有效的治疗方法来对抗复发并提高存活率。
本综述描述了各种 MDB 疾病特征,包括涉及病理生理学的信号机制、相关因果基因、表观遗传学、下游基因/表观基因,以及可能的因果疾病基因/非蛋白编码(nc)RNA/蛋白质轴。此外,还讨论了 MDB 治疗面临的挑战,以及如何利用纳米技术和纳米生物医学来解决这些挑战,列出了可能的治疗选择和未来潜在的治疗方式。