癌症中PI3K信号通路的改变：同一主题的变体
PI3K pathway alterations in cancer: variations on a theme.
作者信息
Yuan T L, Cantley L C
机构信息
Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 2115, USA.
出版信息
Oncogene. 2008 Sep 18;27(41):5497-510. doi: 10.1038/onc.2008.245.
Abstract
The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has led to a surge in the development of PI3K inhibitors. Many of these targeted therapies are currently in clinical trials and show great promise for the treatment of PI3K-addicted tumors. These recent developments call for a re-evaluation of the oncogenic mechanisms behind PI3K pathway alterations. This pathway is unique in that every major node is frequently mutated or amplified in a wide variety of solid tumors. Receptor tyrosine kinases upstream of PI3K, the p110 alpha catalytic subunit of PI3K, the downstream kinase, AKT, and the negative regulator, PTEN, are all frequently altered in cancer. In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions.
摘要
磷酸肌醇3-激酶（PI3K）通路改变在癌症中出现的高频率，导致了PI3K抑制剂开发的激增。目前，许多这类靶向疗法正处于临床试验阶段，对治疗依赖PI3K的肿瘤显示出巨大前景。这些最新进展促使人们重新评估PI3K通路改变背后的致癌机制。该通路的独特之处在于，在多种实体瘤中，其每个主要节点都经常发生突变或扩增。PI3K上游的受体酪氨酸激酶、PI3K的p110α催化亚基、下游激酶AKT以及负调节因子PTEN，在癌症中都经常发生改变。在本综述中，我们将研究这些基因改变的致癌特性，以了解它们是冗余的还是独特的，并提出针对这些基因损伤的治疗策略。
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