Workman Paul, Clarke Paul A, Al-Lazikani Bissan
Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
Oncotarget. 2016 Jan 26;7(4):3658-61. doi: 10.18632/oncotarget.6971.
It is now recognised that genetic, epigenetic and phenotypic heterogeneity within individual human cancers is responsible for therapeutic resistance - knowledge that is having a profound impact on current thinking and experimentation. There has been concern that molecularly targeted therapy is doomed to failure, with resistant clones emerging in response to the Darwinian selective pressure of any drug treatment. However, two studies have shown that the evolution of drug resistance can be restrained by co-administration of a pharmacologic inhibitor of the HSP90 molecular chaperone.
现在人们认识到,个体人类癌症中的基因、表观遗传和表型异质性是导致治疗耐药性的原因——这一认识正在对当前的思维和实验产生深远影响。有人担心分子靶向治疗注定会失败,因为在任何药物治疗的达尔文式选择压力下会出现耐药克隆。然而,两项研究表明,通过联合使用HSP90分子伴侣的药理学抑制剂,可以抑制耐药性的演变。