Advances in Clinical Application of ctDNA Detection in NSCLC

With high morbidity and mortality, lung cancer has become the leading cause of cancer-related death worldwide, of which 85% are non-small-cell lung cancer (NSCLC). Most patients present with advanced disease at diagnosis and 5-year survival rate is no more than 30% due to lack of appropriate screening and early detection. In spite of tissue samples, ctDNA (circulating tumor DNA) is also widely used for molecular profiling to guide the treatment of NSCLC for lots of advantages. This review mainly focuses on the clinical and investigational applications of ctDNA detection in facilitating the personalized therapy of NSCLC. Initially reported by Mandel et al. in 1948M1, cfDNA (cell-free DNA) refers to the acellular, free DNA fragments in circulation (plasma or serum) derived from somatic cells through mechanisms like necrosis, apoptosis and exosome secretion. ctDNA is cfDNA generated by tumor cells, which carries cancer-associated genetic alterations2,3. In 1977, Leon et al. first reported that the level of plasma ctDNA of patients with cancer was significantly higher than that of normal persons4, which was also confirmed in NSCLC5,6. In NSCLC patients, techniques for targetable genetic ctDNA detection have improved from traditional ARMS, HPLC, BEAMing, FISH to new generations of NGS (next generation sequencing), ddPCR and CAPP-Seq etc. Compared with traditional detection methods, NGS shows extraordinary advantages like massively parallel sequencing, lower-inputs, cost-effectivity, ultra-sensitivity and hyper accuracy7,8. The main applications of ctDNA detection in the personalized treatment of NSCLC patients will be discussed in this review.