Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, United States.
Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, United States.
Drug Resist Updat. 2017 Jan;30:48-62. doi: 10.1016/j.drup.2017.02.002. Epub 2017 Feb 21.
Predictive biomarkers for oncology are necessary to accurately identify patients who will benefit from anticancer treatment. Recently approved oncology drugs target discrete molecular aberrations or pathways in tumor cells and consequently are active on a subset of patient population, yet clinical studies have shown that not all biomarker-positive patients respond. The advancement of predictive biomarkers needs to detect novel and evolving drug resistance mechanisms, not only to guide the selection of patient subsets for specific treatments, but to identify new therapeutic targets. Going beyond the "one marker, one drug" model to incorporate genomics, transcriptomics, and receptor status assessments during biomarker-drug co-development can aid in the successful application of molecular marker-based cancer therapy. This review provides the latest update of biomarker-based cancer therapeutics approved by the US Food and Drug Administration. We provide case studies of therapeutics selectively targeting HER2, EGFR, or PD-1/PD-L1 signaling pathways. We also discuss the challenges and promising future directions in the co-development of targeted cancer therapeutics and paired predictive biomarkers.
肿瘤的预测性生物标志物对于准确识别将从抗癌治疗中获益的患者是必要的。最近批准的肿瘤药物针对肿瘤细胞中离散的分子异常或途径，因此仅对一部分患者群体有效，但临床研究表明并非所有生物标志物阳性患者都有响应。预测性生物标志物的发展需要检测新的和不断发展的耐药机制，不仅要指导特定治疗方案的患者亚组选择，还要确定新的治疗靶点。超越“一个标志物，一个药物”的模式，在标志物-药物共同开发过程中纳入基因组学、转录组学和受体状态评估，可以帮助成功应用基于分子标志物的癌症治疗。本文综述了美国食品和药物管理局批准的基于生物标志物的癌症治疗药物的最新进展。我们提供了针对 HER2、EGFR 或 PD-1/PD-L1 信号通路的治疗药物的案例研究。我们还讨论了靶向癌症治疗药物和配对预测性生物标志物共同开发中的挑战和有前景的未来方向。
