Sorber L, Zwaenepoel K, Deschoolmeester V, Van Schil P E Y, Van Meerbeeck J, Lardon F, Rolfo C, Pauwels P
Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Pathology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium.
Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Pathology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium.
Lung Cancer. 2017 May;107:100-107. doi: 10.1016/j.lungcan.2016.04.026. Epub 2016 May 4.
Lung cancer is the predominant cause of cancer-related mortality in the world. The majority of patients present with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Treatment for NSCLC is evolving from the use of cytotoxic chemotherapy to personalized treatment based on molecular alterations. Unfortunately, the quality of the available tumor biopsy and/or cytology material is not always adequate to perform the necessary molecular testing, which has prompted the search for alternatives. This review examines the use of circulating cell-free nucleic acids (cfNA), consisting of both circulating cell-free (tumoral) DNA (cfDNA-ctDNA) and RNA (cfRNA), as a liquid biopsy in lung cancer. The development of sensitive and accurate techniques such as Next-Generation Sequencing (NGS); Beads, Emulsion, Amplification, and Magnetics (BEAMing); and Digital PCR (dPCR), have made it possible to detect the specific genetic alterations (e.g. EGFR mutations, MET amplifications, and ALK and ROS1 translocations) for which targeted therapies are already available. Moreover, the ability to detect and quantify these tumor mutations has enabled the follow-up of tumor dynamics in real time. Liquid biopsy offers opportunities to detect resistance mechanisms, such as the EGFR T790M mutation in the case of EGFR TKI use, at an early stage. Several studies have already established the predictive and prognostic value of measuring ctNA concentration in the blood. To conclude, using ctNA analysis as a liquid biopsy has many advantages and allows for a variety of clinical and investigational applications.
肺癌是全球癌症相关死亡的主要原因。大多数患者表现为局部晚期或转移性非小细胞肺癌（NSCLC）。NSCLC的治疗正在从使用细胞毒性化疗向基于分子改变的个性化治疗发展。不幸的是，可用的肿瘤活检和/或细胞学材料的质量并不总是足以进行必要的分子检测，这促使人们寻找替代方法。本综述探讨了循环游离核酸（cfNA）作为肺癌液体活检的应用，cfNA包括循环游离（肿瘤）DNA（cfDNA-ctDNA）和RNA（cfRNA）。诸如下一代测序（NGS）、磁珠、乳液、扩增和磁性技术（BEAMing）以及数字PCR（dPCR）等灵敏且准确的技术的发展，使得检测那些已有靶向治疗药物的特定基因改变（例如表皮生长因子受体（EGFR）突变、间质-上皮转化因子（MET）扩增以及间变性淋巴瘤激酶（ALK）和原癌基因酪氨酸蛋白激酶ROS1（ROS1）易位）成为可能。此外，检测和定量这些肿瘤突变的能力使得实时跟踪肿瘤动态成为可能。液体活检为早期检测耐药机制提供了机会，例如在使用EGFR酪氨酸激酶抑制剂（TKI）时检测EGFR T790M突变。多项研究已经证实了检测血液中循环肿瘤核酸（ctNA）浓度的预测和预后价值。总之，将ctNA分析用作液体活检具有诸多优势，并允许进行多种临床和研究应用。
