N.N. Petrov Institute of Oncology, St.-Petersburg 197758. Russian Federation.
Curr Pharm Des. 2017;23(32):4794-4806. doi: 10.2174/1381612823666170719110125.
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays. For example, administration of PARP inhibitors is tailored to a comprehensive testing of BRCA1 and BRCA2 genes, and is likely to be supplemented in the future by even more systematic assessment of DNA repair pathways. The detection of an androgenindependent splice-variant of androgen-receptor (AR-V7) in castration-resistant prostate cancer is achieved through the isolation of circulating tumor cells (CTCs). The efficacy of immune check-point inhibitors correlates with the overall mutational tumor load, therefore the companion diagnostic assays may involve genome-wide scanning. Integration of next-generation sequencing (NGS) into clinical oncology is expected to boost the use of predictive tests in the forthcoming years.
目前已有十多种经过批准的癌症药物，其给药方案均根据预测性实验室检测结果制定。这些药物包括：用于内分泌治疗的雌激素和孕激素受体状态检测、用于曲妥珠单抗等 HER2 靶向药物治疗的 HER2 评估、用于肺癌治疗的 EGFR 和 ALK 基因检测、黑色素瘤的 BRAF 分析等。最初的预测性检测依赖于相对简单的实验室程序，而最近的发展则需要更复杂的检测方法。例如，PARP 抑制剂的给药方案是根据 BRCA1 和 BRCA2 基因的全面检测结果制定的，未来可能会通过对 DNA 修复途径进行更系统的评估来补充这种方案。在去势抵抗性前列腺癌中，雄激素受体（AR-V7）的无雄激素剪接变体是通过分离循环肿瘤细胞（CTC）来检测的。免疫检查点抑制剂的疗效与肿瘤的总体突变负荷相关，因此伴随诊断检测可能涉及全基因组扫描。下一代测序（NGS）在肿瘤学中的应用有望在未来几年推动预测性检测的使用。
