摘要
胶质母细胞瘤(IV级星形细胞瘤)是一种侵略性强且无法治愈的脑瘤。它在诊断时,总是表现出广泛的侵略性,且往往涉及大脑的两个半球。最近的研究已经给了我们一个关于胶质母细胞瘤遗传学非常详尽的描述。这些描述绘出了这一疾病在不同患者之间和个别患者身上的高度异质性。这种患者之间的异质性给靶向治疗的设计提出重大挑战。一种方法是识别在胶质母细胞瘤中异常激活的信号通路的常见下游元素的靶点。这里我们论述非典型蛋白激酶C族中PKCι可能发挥这一作用的证据。我们目前对于PKCι激活机制的理解还在讨论并与胶质母细胞瘤的常见遗传改变有关。数据表明,PKCι在胶质母细胞瘤病理学的多个方面的重要作用也在论述中。最后,关于PKCι在正常大脑运行中作用的数据也在讨论,以了解PKCι抑制在中枢神经系统中潜在的副作用。
关键词: 非典型蛋白激酶C,胶质母细胞瘤,胶质瘤,PKCι, PKCζ, PTEN
图形摘要
Current Cancer Drug Targets
Title:Atypical PKCι as Target for Glioblastoma Therapy
Volume: 15 Issue: 2
Author(s): Ian A.J. Lorimer
Affiliation:
关键词: 非典型蛋白激酶C,胶质母细胞瘤,胶质瘤,PKCι, PKCζ, PTEN
摘要: Glioblastoma (grade IV astrocytoma) is an aggressive and incurable form of brain tumor. It invariably shows extensive invasion at the time of diagnosis, often involving both hemispheres. Recent studies have given us a very detailed picture of glioblastoma genetics. These paint a picture of a disease with extensive heterogeneity, both between patients and within individual patients. This within patient heterogeneity presents a major challenge in the design of targeted therapies. One approach is to identify targets that are common downstream elements in signaling pathways that are aberrantly activated in glioblastoma. Here we review the evidence that the atypical protein kinase C family member PKCι may fulfill this role. Our current understanding of PKCι activation mechanisms is discussed and related to common genetic changes in glioblastoma. The data showing an essential role for PKCι in multiple aspects of glioblastoma pathology are also reviewed. Finally, data on the role of PKCι in normal brain function are reviewed for insights into potential side effects of PKCι inhibition in the central nervous system.
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Cite this article as:
Ian A.J. Lorimer , Atypical PKCι as Target for Glioblastoma Therapy, Current Cancer Drug Targets 2015; 15 (2) . https://dx.doi.org/10.2174/1568009615666150201220250
DOI https://dx.doi.org/10.2174/1568009615666150201220250 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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