Chan Hiu Ting, Chin Yoon Ming, Low Siew-Kee
Project for Development of Liquid Biopsy Diagnosis, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
Cancer Precision Medicine, Inc., Kawasaki 213-0012, Japan.
Cancers (Basel). 2022 Jul 4;14(13):3275. doi: 10.3390/cancers14133275.
Genomic profiling using tumor biopsies remains the standard approach for the selection of approved molecular targeted therapies. However, this is often limited by its invasiveness, feasibility, and poor sample quality. Liquid biopsies provide a less invasive approach while capturing a contemporaneous and comprehensive tumor genomic profile. Recent advancements in the detection of circulating tumor DNA (ctDNA) from plasma samples at satisfactory sensitivity, specificity, and detection concordance to tumor tissues have facilitated the approval of ctDNA-based genomic profiling to be integrated into regular clinical practice. The recent approval of both single-gene and multigene assays to detect genetic biomarkers from plasma cell-free DNA (cfDNA) as companion diagnostic tools for molecular targeted therapies has transformed the therapeutic decision-making procedure for advanced solid tumors. Despite the increasing use of cfDNA-based molecular profiling, there is an ongoing debate about a 'plasma first' or 'tissue first' approach toward genomic testing for advanced solid malignancies. Both approaches present possible advantages and disadvantages, and these factors should be carefully considered to personalize and select the most appropriate genomic assay. This review focuses on the recent advancements of cfDNA-based genomic profiling assays in advanced solid tumors while highlighting the major challenges that should be tackled to formulate evidence-based guidelines in recommending the 'right assay for the right patient at the right time'.
使用肿瘤活检进行基因组分析仍然是选择已获批分子靶向疗法的标准方法。然而，这一方法常常受到其侵入性、可行性以及样本质量差的限制。液体活检提供了一种侵入性较小的方法，同时能够获取同步且全面的肿瘤基因组图谱。近期，在从血浆样本中检测循环肿瘤DNA（ctDNA）方面取得了进展，其灵敏度、特异性以及与肿瘤组织的检测一致性令人满意，这推动了基于ctDNA的基因组分析获批纳入常规临床实践。近期，单基因和多基因检测均获批用于从血浆游离DNA（cfDNA）中检测基因生物标志物，作为分子靶向疗法的伴随诊断工具，这改变了晚期实体瘤的治疗决策流程。尽管基于cfDNA的分子分析应用越来越广泛，但对于晚期实体恶性肿瘤的基因组检测，是采用“血浆优先”还是“组织优先”的方法仍存在争议。两种方法都有各自的优缺点，在个性化选择最合适的基因组检测时，应仔细考虑这些因素。本综述重点关注基于cfDNA的基因组分析检测在晚期实体瘤中的最新进展，同时强调在制定基于证据的指南以推荐“在正确的时间为正确的患者选择正确的检测”时需要应对的主要挑战。
