Department of Clinical Pharmacology, Levine Cancer Institute, Carolinas HealthCare System, 1021 Morehead Medical Drive, Charlotte, NC 28203, USA.
Pharmacogenomics. 2014 Jan;15(1):79-93. doi: 10.2217/pgs.13.227.
Given the interpatient biological heterogeneity and narrow therapeutic index of anticancer drugs, a practical method for personalizing cancer therapy is essential. Genotype-guided cancer therapy will provide an optimal approach to normalize systemic drug exposures, predict drug toxicities and/or enrich clinical efficacy. To date, over a dozen anticancer drugs approved by the US FDA require labeling regarding pharmacogenetic biomarkers (both germline and somatic). Many, but not all, have prospective, genotype-guided evidence-based data. Optimizing output from retrospective, prospective, cost-effectiveness and adaptive biomarker driven clinical trials will help drive the success of personalized cancer therapy. This review will discuss prospective genotype-guided clinical trials in patients with solid tumors and address barriers in clinical translation.
鉴于抗肿瘤药物的患者间生物学异质性和治疗指数狭窄，个性化癌症治疗的实用方法至关重要。基于基因型的癌症治疗将为使全身药物暴露正常化、预测药物毒性和/或富集临床疗效提供最佳方法。迄今为止，美国 FDA 批准的十几种抗肿瘤药物需要对遗传和体细胞的药物基因组生物标志物进行标签说明。许多药物（但不是全部）具有基于前瞻性基因型指导的证据数据。优化回顾性、前瞻性、成本效益和适应性生物标志物驱动的临床试验的结果将有助于推动个性化癌症治疗的成功。本文将讨论实体瘤患者的前瞻性基因型指导临床试验，并探讨临床转化中的障碍。
