对靶向治疗的耐药性：似曾相识的感觉再次出现。
Drug resistance to targeted therapies: déjà vu all over again.
作者信息
Groenendijk Floris H, Bernards René
机构信息
Division of Molecular Carcinogenesis, Cancer Genomics Center Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Division of Molecular Carcinogenesis, Cancer Genomics Center Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
出版信息
Mol Oncol. 2014 Sep 12;8(6):1067-83. doi: 10.1016/j.molonc.2014.05.004. Epub 2014 May 21.
Abstract
A major limitation of targeted anticancer therapies is intrinsic or acquired resistance. This review emphasizes similarities in the mechanisms of resistance to endocrine therapies in breast cancer and those seen with the new generation of targeted cancer therapeutics. Resistance to single-agent cancer therapeutics is frequently the result of reactivation of the signaling pathway, indicating that a major limitation of targeted agents lies in their inability to fully block the cancer-relevant signaling pathway. The development of mechanism-based combinations of targeted therapies together with non-invasive molecular disease monitoring is a logical way forward to delay and ultimately overcome drug resistance development.
摘要
靶向抗癌疗法的一个主要局限性是内在或获得性耐药。本综述强调了乳腺癌内分泌治疗耐药机制与新一代靶向癌症治疗中所见耐药机制的相似性。对单一药物癌症治疗的耐药通常是信号通路重新激活的结果，这表明靶向药物的一个主要局限性在于它们无法完全阻断与癌症相关的信号通路。开发基于机制的靶向治疗组合并结合非侵入性分子疾病监测是延缓并最终克服耐药性发展的合理前进方向。
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本文引用的文献
1
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Cell Rep. 2014 Apr 10;7(1):86-93. doi: 10.1016/j.celrep.2014.02.045. Epub 2014 Mar 27.
2
Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma.黑色素瘤中 BRAF(V600E) 抑制的可逆和适应性耐药。
Nature. 2014 Apr 3;508(7494):118-22. doi: 10.1038/nature13121. Epub 2014 Mar 26.
3
Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer.预处理的晚期雌激素受体阳性乳腺癌中组成型活性雌激素受体-α 突变的出现。
Clin Cancer Res. 2014 Apr 1;20(7):1757-1767. doi: 10.1158/1078-0432.CCR-13-2332. Epub 2014 Jan 7.
4
Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA.动态调节染色体外突变 EGFR DNA 介导的靶向治疗耐药性。
Science. 2014 Jan 3;343(6166):72-6. doi: 10.1126/science.1241328. Epub 2013 Dec 5.
5
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6
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