Drug Resistance Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
Nat Rev Cancer. 2013 Oct;13(10):714-26. doi: 10.1038/nrc3599.
Resistance to chemotherapy and molecularly targeted therapies is a major problem facing current cancer research. The mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to therapies that are designed to be selective for specific molecular targets share many features, such as alterations in the drug target, activation of prosurvival pathways and ineffective induction of cell death. With the increasing arsenal of anticancer agents, improving preclinical models and the advent of powerful high-throughput screening techniques, there are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.
化疗和分子靶向治疗耐药是当前癌症研究面临的主要问题。对“经典”细胞毒化疗药物和旨在针对特定分子靶点的治疗药物的耐药机制具有许多共同特征，例如药物靶点的改变、存活途径的激活以及细胞死亡的无效诱导。随着抗癌药物的不断增加，以及临床前模型的改进和高通量筛选技术的出现，现在有了前所未有的机会通过对合理的治疗药物组合的临床评估以及使用预测性生物标志物来进行患者分层，从而理解和克服耐药性。
