Peking University Fifth School of Clinical Medicine, National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China; National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, PR China.
National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, PR China.
Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188363. doi: 10.1016/j.bbcan.2020.188363. Epub 2020 Apr 8.
Targeted molecular therapies have markedly improved the therapeutic management of lung cancer, while the discovery of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the clinical benefit of targeted therapies is limited by the eventual emergence of resistance. Identifying and monitoring the underlying mechanism of EGFR-TKI resistance could lead to more precise therapy and advances in treatment. Presently, tissue biopsy remains the gold standard for genotyping but it is limited by sampling bias, lack of available tissue, and potential complications. Analysis of circulating tumour DNA (ctDNA) may overcome the current limitations of tissue biopsies and provide a comprehensive landscape of the resistance mechanisms in a minimally invasive manner. Well-developed, analytically valid detection technologies are prerequisites for integrating ctDNA detection into clinical cancer management. Here, we provide an overview of available methodologies for ctDNA detection and we also discuss the potential clinical applications of ctDNA to monitor the resistance mechanisms.
靶向分子治疗显著改善了肺癌的治疗管理，而表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的发现彻底改变了非小细胞肺癌（NSCLC）的治疗方法。然而，靶向治疗的临床获益受到耐药性的最终出现的限制。确定和监测 EGFR-TKI 耐药的潜在机制可能会导致更精确的治疗和治疗进展。目前，组织活检仍然是基因分型的金标准，但它受到采样偏差、组织不可用和潜在并发症的限制。循环肿瘤 DNA（ctDNA）的分析可能会克服目前组织活检的局限性，并以微创的方式提供耐药机制的全面情况。成熟的、具有分析学有效性的检测技术是将 ctDNA 检测纳入临床癌症管理的前提。在这里，我们提供了 ctDNA 检测的现有方法学概述，并讨论了 ctDNA 监测耐药机制的潜在临床应用。
