Ferreira Bibiana I, Lie Maria K, Engelsen Agnete S T, Machado Susana, Link Wolfgang, Lorens James B
Centre for Biomedical Research (CBMR) , University of Algarve , Campus of Gambelas, Building 8, room 2.22 , 8005-139 Faro , Portugal.
Regenerative Medicine Program , Department of Biomedical Sciences and Medicine , University of Algarve , Campus de Gambelas , 8005-139 Faro , Portugal . Email:
Medchemcomm. 2016 Oct 21;8(1):53-66. doi: 10.1039/c6md00394j. eCollection 2017 Jan 1.
Intrinsic and acquired resistance to conventional and targeted therapeutics is a fundamental reason for treatment failure in many cancer patients. Targeted approaches to overcome chemoresistance as well as resistance to targeted approaches require in depth understanding of the underlying molecular mechanisms. The anti-cancer activity of a drug can be limited by a broad variety of molecular events at different levels of drug action in a cell-autonomous and non-cell-autonomous manner. This review summarizes recent insights into the adaptive mechanisms used by tumours to resist therapy including cellular phenotypic plasticity, dynamic alterations of the tumour microenvironment, activation of redundant signal transduction pathways, modulation of drug target expression levels, and exploitation of pro-survival responses.
对传统疗法和靶向疗法的内在和获得性耐药是许多癌症患者治疗失败的根本原因。克服化疗耐药以及靶向治疗耐药的靶向方法需要深入了解潜在的分子机制。药物的抗癌活性可能受到细胞自主和非细胞自主方式下不同药物作用水平的多种分子事件的限制。本综述总结了肿瘤用于抵抗治疗的适应性机制的最新见解，包括细胞表型可塑性、肿瘤微环境的动态改变、冗余信号转导通路的激活、药物靶点表达水平的调节以及促生存反应的利用。
