Clinical application of liquid biopsy based on circulating tumor DNA in non-small cell lung cancer

Abstract

Lung cancer is a widely occurring and deadly malignancy, with high prevalence rates in China and across the globe. Specifically, non-small cell lung cancer (NSCLC) represents about 85% of all lung cancer cases. The 5-year disease-free survival rate after surgery for stage IB-IIIB NSCLC patients (disease-free survival, DFS) has notably declined from 73% to 13%. Early detection of abnormal cancer molecules and subsequent personalized treatment plans are the most effective ways to address this problem. Liquid biopsy, surprisingly, enables safe, accurate, non-invasive, and dynamic tracking of disease progression. Among the various modalities, circulating tumor DNA (ctDNA) is the most commonly used liquid biopsy modality. ctDNA serves as a credible “liquid biopsy” diagnostic tool that, to a certain extent, overcomes tumor heterogeneity and harbors genetic mutations in malignancies, thereby providing early information on tumor genetic alterations. Despite considerable academic interest in the clinical significance of ctDNA, consensus on its utility remains lacking. In this review, we assess the role of ctDNA testing in the diagnosis and management of NSCLC as a reference for clinical intervention in this disease. Lastly, we examine future directions to optimize ctDNA for personalized therapy.

Liquid biopsy in non-small cell lung cancer: a meta-analysis of state-of-the-art and future perspectives

“…Of note, even if in high-stage tumours LB sensitivity is high, it does not reach the same performance as TB. To increase LB sensitivity, blood samples could be repeated at different times or other biological fluids (e.g., saliva, urine, sputum) could be analysed as an alternative or in combination with plasma ( Lino et al, 2023 ; Xin et al, 2023 ). On the other hand, LB does not seem to be indicated for early-stage tumours, showing a high rate of FN results, possibly due to the scarcity/lack of tDNA shed into circulation, or to the technical limits of current detection methods ( Qiu et al, 2023 ).…”

Biomarkers for Early Cancer Detection: A Landscape View of Recent Advancements, Spotlighting Pancreatic and Liver Cancers

“…Liquid biopsy techniques began to gain attention for their potential to detect ctDNA and other biomarkers in blood samples, providing safe, accurate, noninvasive, and dynamic tracking of disease progression. 80 Further, advances in single-cell sequencing allowed for a deeper understanding of tumor heterogeneity and the identification of rare cancer cells. 81 Immune-related biomarkers, such as PD-L1 expression, gained prominence with the advent of immunotherapy for cancer treatment.…”

“…The Human Genome Project and The Cancer Genome Atlas (TCGA) project provided valuable insights into the genetic mutations and alterations associated with various cancers. Liquid biopsy techniques began to gain attention for their potential to detect ctDNA and other biomarkers in blood samples, providing safe, accurate, non-invasive, and dynamic tracking of disease progression …”