Dysregulation of growth factor cell signaling is a major driver of most human cancers. This has led to development of numerous drugs targeting protein kinases, with demonstrated efficacy in the treatment of a wide spectrum of cancers. Despite their high initial response rates and survival benefits, the majority of patients eventually develop resistance to these targeted therapies. This review article discusses examples of established mechanisms of drug resistance to anticancer therapies, including drug target mutations or gene amplifications, emergence of alternate signaling pathways, and pharmacokinetic variation. This reveals a role for pharmacogenomic analysis to identify and monitor for resistance, with possible therapeutic strategies to combat chemoresistance.

生长因子细胞信号传导失调是大多数人类癌症的主要驱动因素。这导致了许多针对蛋白激酶的药物的开发，并在治疗多种癌症方面显示出疗效。尽管初始反应率和生存获益较高，但大多数患者最终会对这些靶向治疗产生耐药性。这篇综述文章讨论了抗癌治疗耐药机制的例子，包括药物靶点突变或基因扩增、替代信号通路的出现和药代动力学变异。这揭示了药物基因组学分析在识别和监测耐药性方面的作用，以及对抗化疗耐药性的可能治疗策略。