Resisting Resistance: Targeted Therapies in Lung Cancer.

Resisting Resistance: Targeted Therapies in Lung Cancer.
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DOI:
10.1016/j.trecan.2016.05.010
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发表时间:
2016-07
期刊:
影响因子:
18.4
通讯作者:
Shaw, Alice T.
Shaw, Alice T.
中科院分区:
医学1区
文献类型:
--
作者:
Lin, Jessica J.;Shaw, Alice T.

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耐药性不可避免地限制了包括酪氨酸激酶抑制剂(TKI)在内的所有靶向治疗的疗效。了解TKI耐药性的生物学基础是成功开发未来治疗策略的关键。传统上,TKI耐药的机制一直被视为二分法透镜。肿瘤细胞是TKI敏感性或TKI难治性的,表现出内在或获得性抗性,并在靶点内或靶点外积累改变以促进其存活。这种分类有助于我们理解复杂的生物学,但可能过于简单化。最近的研究强调了TKI耐药的多方面、遗传异质性,其随着治疗的变化而动态演变。在这篇综述中,我们提供了一个广泛的框架,以了解癌基因驱动的肺癌中发挥作用的多种耐药机制。
Drug resistance inevitably limits the efficacy of all targeted therapies including tyrosine kinase inhibitors (TKIs). Understanding the biological underpinnings of TKI resistance is key to the successful development of future therapeutic strategies. Traditionally, mechanisms of TKI resistance have been viewed under a dichotomous lens. Tumor cells are TKI-sensitive or TKI-refractory, exhibit intrinsic or acquired resistance, and accumulate alterations within or outside the target to promote their survival. Such classifications facilitate our comprehension of an otherwise complex biology, but are likely an oversimplification. Recent studies underscore the multifaceted, genetically heterogeneous nature of TKI resistance, which evolves dynamically with changes in therapy. In this Review, we provide a broad framework for understanding the diverse mechanisms of resistance at play in oncogene-driven lung cancers.
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