摘要
髓母细胞瘤是最常见的恶性儿童脑肿瘤,且预后较差。目前迫切需要开发新的靶向性治疗髓母细胞瘤的方法,这将导致对该病分子水平上的更深入理解。髓母细胞瘤被认为是一种异质性疾病,未发现复发性癌基因突变。尽管迄今许多描述的突变影响主要的细胞内信号通路,例如音猬 (SHH)和Wnt/β-catenin。PI3K/AKT/mTOR (PAM)信号通路控制关键的细胞反应如细胞生长、增殖、存活、迁移和代谢。在过去的几十年中,人们认识到,这种细胞内信号通路在恶性脑瘤中由遗传和外遗传改变频繁激活,包括髓母细胞瘤。临床实验已经开始评估针对恶性脑瘤中该通路的靶向制剂的安全性和有效性。由于 PAM信号通路的复杂性,对新治疗方法的发展仍有明显的困难。对开发针对癌症病人的有效治疗方法的未来挑战包括预测生物标志物的开发和针对多信号转导途径的结合治疗方法。在这篇综述文章中,我们将总结髓母细胞瘤中关于 PAM信号作用的现有知识,并且讨论有关目前正在被评估的针对这一通路的靶向制剂的策略。
关键词: AKT,临床试验,髓母细胞瘤,mTOR,磷酸肌醇3-激酶,PTEN。
Current Molecular Medicine
Title:Targeting the PI3K/AKT/mTOR Signaling Pathway in Medulloblastoma
Volume: 15 Issue: 1
Author(s): V. Dimitrova and A. Arcaro
Affiliation:
关键词: AKT,临床试验,髓母细胞瘤,mTOR,磷酸肌醇3-激酶,PTEN。
摘要: Medulloblastoma is the most common malignant childhood brain tumor and is associated with a poor outcome. There is an urgent need to develop novel targeted therapeutic approaches for medulloblastoma, which will arise from an enhanced understanding of the disease at the molecular level. Medulloblastoma has been recognized to be a heterogeneous disease, and no recurrent cancer gene mutations have been found, although many of the mutations described so far affect key intracellular signaling pathways, such as sonic hedgehog (SHH) and Wnt/β-catenin. The PI3K/AKT/mTOR (PAM) signaling pathway controls key cellular responses, such as cell growth and proliferation, survival, migration and metabolism. Over the last decades, it has been recognized that this intracellular signaling pathway is frequently activated by genetic and epigenetic alterations in malignant brain tumors, including medulloblastoma. Clinical trials have started to evaluate the safety and efficacy of agents targeting this pathway in malignant brain tumors. Due to the complexity of the PAM signaling pathway, there remain significant difficulties in the development of novel therapeutic approaches. The future challenges in developing effective treatments for cancer patients include the development of predictive biomarkers and combinatorial approaches to effectively target multiple signal transduction pathways. In this review article, we will summarize the current knowledge about the role of PAM signaling in medulloblastoma and discuss the strategies that are currently being evaluated with targeted agents against this pathway.
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Cite this article as:
V. Dimitrova and A. Arcaro , Targeting the PI3K/AKT/mTOR Signaling Pathway in Medulloblastoma, Current Molecular Medicine 2015; 15 (1) . https://dx.doi.org/10.2174/1566524015666150114115427
DOI https://dx.doi.org/10.2174/1566524015666150114115427 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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