Raei Negin, Safaralizadeh Reza, Latifi-Navid Saeid
Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Expert Rev Mol Diagn. 2023 Jul-Dec;23(12):1209-1220. doi: 10.1080/14737159.2023.2268008. Epub 2023 Dec 15.
Advances in genomics have facilitated the application of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) in phase II and phase III clinical trials. The various mutations of cfDNA/ctDNA have been correlated with clinical features. Advances in next-generation sequencing (NGS) and digital droplet PCR have paved the way for identifying cfDNA/ctDNA mutations.
Herein, the biology of ctDNA and its function in clinical application in metastasis, which may lead to improved clinical management of metastatic cancer patients, are comprehensively reviewed.
Metastatic cancer ctDNA shows the greatest frequency of mutations in TP53, HER-2, KRAS, and EGFR genes (alteration frequency of > 50%). Therefore, identifying key mutations frequently present in metastatic cancers can help identify patients with pre-malignant tumors before cancer progression. Studying ctDNA can help determine the prognosis and select appropriate treatments for affected patients. Nevertheless, the obstacles to detecting and analyzing ctDNA should be addressed before translation into routine practice. Also, more clinical trials should be conducted to study the significance of ctDNA in commonly diagnosed malignancies. Given the recent advances in personalized anti-neoplastic treatments, further studies are needed to detect a panel of ctDNA and patient-specific ctDNA for various cancers.
基因组学的进展促进了游离DNA(cfDNA)和循环肿瘤DNA(ctDNA)在II期和III期临床试验中的应用。cfDNA/ctDNA的各种突变已与临床特征相关联。下一代测序(NGS)和数字液滴PCR的进展为识别cfDNA/ctDNA突变铺平了道路。
本文全面综述了ctDNA的生物学特性及其在转移临床应用中的功能,这可能会改善转移性癌症患者的临床管理。
转移性癌症ctDNA在TP53、HER-2、KRAS和EGFR基因中的突变频率最高(改变频率>50%)。因此,识别转移性癌症中常见的关键突变有助于在癌症进展前识别癌前肿瘤患者。研究ctDNA有助于确定预后并为受影响患者选择合适的治疗方法。然而,在将ctDNA检测和分析转化为常规实践之前,应解决相关障碍。此外,应开展更多临床试验来研究ctDNA在常见诊断恶性肿瘤中的意义。鉴于个性化抗肿瘤治疗的最新进展,需要进一步研究以检测各种癌症的一组ctDNA和患者特异性ctDNA。