Cell-free circulating tumor DNA in plasma/serum of non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is the common type of lung cancer, which is the leading cause of cancer death throughout the world. Most patients were diagnosed too late for curative treatment. So, it is necessary to develop a minimal invasive method to identify NSCLC at an early stage. In recent years, cell-free circulating tumor DNA (ctDNA) has attracted increasing attention as a potential tumor marker for its minimal invasive, convenient, and easily accepted properties. The amount of ctDNA in plasma or serum was significantly higher in NSCLC patients than that in healthy controls or patients with benign diseases. Furthermore, many studies have proved an association among tumor stage, tumor grade, lymph node involvement, the number of metastatic sites, tumor response, survival outcome, and the ctDNA levels. Many genetic changes, such as gene mutation, loss of heterozygosity, microsatellite instability, and gene methylation were also found in ctDNA in NSCLC patients. These findings demonstrated that the ctDNA could serve as a viable tool to monitor NSCLC and prompted us to find more sensitive and specific biomarkers for clinical practice, especially monitor these cases with at least one known gene abnormality. Here, we reviewed the evidence of ctDNA in NSCLC and consider possible future applications in patient management.

Circulating cell-free DNA as a prognostic and predictive biomarker in non-small cell lung cancer

“…Besides, the amount of cfDNA in the blood was significantly higher in NSCLC patients than that in healthy controls [9, 48]. What's more, cfDNA levels were associated with tumor volume, tumor stage, lymph node involvement and tumor responses [13]. Newman et al found that levels of cfDNA significantly correlated with tumor volume and provided earlier response assessment than radiographic approaches [49].…”

“…It has been shown that the diagnostic accuracy of quantitative analysis of cfDNA is not lower than conventional serum biomarkers for lung cancer screening [12]. Furthermore, cancer-associated genetic alterations, such as point mutations, deletions, and copy number variations, can be detected in cfDNA [13]. In NSCLC, many studies have investigated the diagnostic accuracy of cfDNA for detecting epithermal growth factor receptor ( EGFR ) mutation [14–16].…”

Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer

“…Indeed, significant progress was not made until recent 10 years with the advent of NGS technology in combination with the early findings of CGP, which significantly improved the sensitivity and specificity of ctDNA detection [13, 20]. Subsequently, research in this field has entered a “golden age” in which the huge potential of ctDNA investigations in tumor diagnosis and treatment is becoming ever clear [2, 21–24]. …”

Overcoming crizotinib resistance in ALK-rearranged NSCLC with the second-generation ALK-inhibitor ceritinib

“…Recently, a study by Nie et al demonstrated how cell-free circulating DNA could be used to genotype NSCLC tumors. [53] These results suggest that non-invasive testing of blood samples from NSCLC patients could be used to accurately genotype the recurrent tumors, thereby identifying the mutations responsible for recurrence. Also, monitoring these patients throughout their treatment by repeatedly testing for crizotinib-resistant ALK DNA in their blood plasma could help to anticipate recurrence.…”