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靶向人类激酶组用于癌症治疗:当前观点

Targeting the human kinome for cancer therapy: current perspectives.

作者信息

Zhang Luxi, Daly Roger J

机构信息

Garvan Institute of Medical Research, Australia.

出版信息

Crit Rev Oncog. 2012;17(2):233-46. doi: 10.1615/critrevoncog.v17.i2.70.

Abstract

As highlighted by other articles in this review issue, great progress has been made in the development of targeted treatment modalities directed against particular oncogenic kinases, and the translation of these therapies into the clinic. However, recent data from cancer genome sequencing projects indicate that the spectrum of kinases that contribute to cancer progression is wider than previously imagined, and as international projects in this area gather momentum, it appears likely that further kinase oncogenes will be identified, and the roles of previously characterized ones will be extended to subsets of additional cancers. In addition, complementary approaches such as functional genomics and mass spectrometry (MS)-based proteomics are providing important insights into the functional roles played by specific kinases in particular cancers, the dependency of these roles on genetic background, how altered kinase regulation perturbs intracellular signaling networks, and how the latter respond to targeted agents that target the kinase in question. While other articles in this issue focus on individual cancer-associated kinases and their therapeutic targeting, the aim of this review is to take a broader perspective regarding our current knowledge of the cancer kinome and how this can be expanded and exploited for clinical utility.

摘要

正如本期综述中的其他文章所强调的,在针对特定致癌激酶的靶向治疗方法的开发以及这些疗法向临床的转化方面已经取得了巨大进展。然而,癌症基因组测序项目的最新数据表明,促成癌症进展的激酶谱比之前想象的要广泛,随着该领域国际项目的推进,似乎有可能会鉴定出更多的激酶致癌基因,并且之前已鉴定激酶的作用会扩展到其他癌症亚型。此外,诸如功能基因组学和基于质谱(MS)的蛋白质组学等互补方法,正在为特定激酶在特定癌症中所起的功能作用、这些作用对遗传背景的依赖性、激酶调节改变如何扰乱细胞内信号网络以及后者如何响应针对相关激酶的靶向药物提供重要见解。虽然本期的其他文章聚焦于个别癌症相关激酶及其治疗靶向,但本综述的目的是从更广泛的角度审视我们目前对癌症激酶组的了解,以及如何扩展并利用这些知识用于临床应用。

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