O'Connor Robert, Clynes Martin, Dowling Paul, O'Donovan Norma, O'Driscoll Lorraine
Dublin City University, National Institute for Cellular Biotechnology (NICB), Dublin 9, Ireland.
Expert Opin Drug Metab Toxicol. 2007 Dec;3(6):805-17. doi: 10.1517/17425255.3.6.805.
Treatment resistance, whether inherent or acquired, is a major problem reducing the activity of conventional and newer, molecularly targeted, cancer drugs. A more complex picture of the causes and contributions of specific forms of resistance is now emerging through application of pharmacological, proteomic and gene expression technologies and we have entered an exciting time where new molecular research tools are being applied not only to characterise the causes of such resistance, but to identify rational new treatments and treatment combinations that are being rapidly translated to clinical evaluations with increasing success. This review outlines many of the contributing causes of resistance to established cytotoxics and to the new breed of molecularly targeted agents, both monoclonal antibodies and small molecules, and the research methods being used to wage war on resistant cancer.
耐药性，无论是固有耐药还是获得性耐药，都是一个重大问题，它降低了传统抗癌药物以及更新的分子靶向抗癌药物的活性。通过应用药理学、蛋白质组学和基因表达技术，关于特定耐药形式的原因和作用的更复杂情况正在显现出来。我们已经进入了一个令人兴奋的时代，新的分子研究工具不仅被用于表征这种耐药性的原因，还被用于识别合理的新治疗方法和治疗组合，这些方法正迅速转化为临床评估，并越来越成功。这篇综述概述了对已确立的细胞毒性药物以及新型分子靶向药物（包括单克隆抗体和小分子药物）产生耐药性的许多促成因素，以及用于对抗耐药性癌症的研究方法。
