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癌基因成瘾:治疗反应、耐药性途径及治愈路线图

Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure.

作者信息

Pagliarini Raymond, Shao Wenlin, Sellers William R

机构信息

Department of Oncology, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.

Department of Oncology, Novartis Institutes for BioMedical Research, Cambridge, MA, USA

出版信息

EMBO Rep. 2015 Mar;16(3):280-96. doi: 10.15252/embr.201439949. Epub 2015 Feb 13.

Abstract

A key goal of cancer therapeutics is to selectively target the genetic lesions that initiate and maintain cancer cell proliferation and survival. While most cancers harbor multiple oncogenic mutations, a wealth of preclinical and clinical data supports that many cancers are sensitive to inhibition of single oncogenes, a concept referred to as 'oncogene addiction'. Herein, we describe the clinical evidence supporting oncogene addiction and discuss common mechanistic themes emerging from the response and acquired resistance to oncogene-targeted therapies. Finally, we suggest several opportunities toward exploiting oncogene addiction to achieve curative cancer therapies.

摘要

癌症治疗的一个关键目标是选择性地靶向引发并维持癌细胞增殖和存活的基因损伤。虽然大多数癌症含有多种致癌突变,但大量临床前和临床数据支持许多癌症对单一癌基因的抑制敏感,这一概念被称为“癌基因成瘾”。在此,我们描述支持癌基因成瘾的临床证据,并讨论针对癌基因靶向治疗的反应和获得性耐药中出现的常见机制主题。最后,我们提出了利用癌基因成瘾实现癌症治愈性治疗的几个机会。

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