Liquid Biopsy for Therapy Monitoring in Early-stage Non-small Cell Lung Cancer

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2021 Jun 2

PMID 34074295

Citations 52

Authors

Misako Nagasaka

Mohammed Hafiz Uddin

Mohammed Najeeb Al-Hallak

Sarah Rahman

Suresh Balasubramanian

Ammar Sukari

Asfar S Azmi

Affiliations

Soon will be listed here.

Abstract

Liquid biopsy is now considered a valuable diagnostic tool for advanced metastatic non-small cell lung cancer (NSCLC). In NSCLC, circulating tumor DNA (ctDNA) analysis has been shown to increase the chances of identifying the presence of targetable mutations and has been adopted by many clinicians owing to its low risk. Serial monitoring of ctDNA may also help assess the treatment response or for monitoring relapse. As the presence of detectable plasma ctDNA post-surgery likely indicates residual tumor burden, studies have been performed to quantify plasma ctDNA to assess minimal residual disease (MRD) in early-stage resected NSCLC. Most data on utilizing liquid biopsy for monitoring MRD in early-stage NSCLC are from small-scale studies using ctDNA. Here, we review the recent research on liquid biopsy in NSCLC, not limited to ctDNA, and focus on novel methods such as micro RNAs (miRNA) and long non-coding (lncRNA).

Citing Articles

The NcRNA/Wnt axis in lung cancer: oncogenic mechanisms, remarkable indicators and therapeutic targets.

Zhong Y, He J, Huang C, Lai H, Li X, Zheng C J Transl Med. 2025; 23(1):326.

PMID: 40087753 DOI: 10.1186/s12967-025-06326-4.

Predictive Significance of Glycosyltransferase-Related lncRNAs in Endometrial Cancer: A Comprehensive Analysis and Experimental Validation.

Shen X, Liu Y, Zhang J, Zhou T, Zhang Q, Dong K ACS Omega. 2025; 10(8):8023-8041.

PMID: 40060793 PMC: 11886429. DOI: 10.1021/acsomega.4c09071.

Potential applications of gene expression profiles obtained from circulating extracellular vesicles in breast cancer.

Gupta A, Bhardwaj S, Ghorai S, Ahmed R, Agarwal S, Mukherjee G J Liq Biopsy. 2025; 7:100287.

PMID: 40027231 PMC: 11863812. DOI: 10.1016/j.jlb.2025.100287.

Liquid biopsy for monitoring minimal residual disease in localized and locally-advanced non-small cell lung cancer after radical-intent treatment.

Aguilar H, Lopez-Roldan B, Vilalta-Lacarra A, Alkorta-Aranburu G, Claramunt R, Lopez-Guerrero J J Liq Biopsy. 2025; 4:100145.

PMID: 40027142 PMC: 11863883. DOI: 10.1016/j.jlb.2024.100145.

Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.

Bi L, Wang X, Li J, Li W, Wang Z MedComm (2020). 2025; 6(3):e70080.

PMID: 39991629 PMC: 11843169. DOI: 10.1002/mco2.70080.

References

Wang S, Zhang K, Tan S, Xin J, Yuan Q, Xu H . Circular RNAs in body fluids as cancer biomarkers: the new frontier of liquid biopsies. Mol Cancer. 2021; 20(1):13. PMC: 7798340. DOI: 10.1186/s12943-020-01298-z. View

Nordmann Winther T, Bang-Berthelsen C, Heiberg I, Pociot F, Hogh B . Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B. PLoS One. 2013; 8(3):e58236. PMC: 3587589. DOI: 10.1371/journal.pone.0058236. View

Lv P, Yang S, Liu W, Qin H, Tang X, Wu F . Circulating plasma lncRNAs as novel markers of EGFR mutation status and monitors of epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Thorac Cancer. 2019; 11(1):29-40. PMC: 6938758. DOI: 10.1111/1759-7714.13216. View

Lo Y, Zhang J, Leung T, Lau T, Chang A, Hjelm N . Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet. 1999; 64(1):218-24. PMC: 1377720. DOI: 10.1086/302205. View

Frampton G, Fichtenholtz A, Otto G, Wang K, Downing S, He J . Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013; 31(11):1023-31. PMC: 5710001. DOI: 10.1038/nbt.2696. View

Kato S, Krishnamurthy N, Banks K, De P, Williams K, Williams C . Utility of Genomic Analysis In Circulating Tumor DNA from Patients with Carcinoma of Unknown Primary. Cancer Res. 2017; 77(16):4238-4246. PMC: 5729906. DOI: 10.1158/0008-5472.CAN-17-0628. View

De Rubis G, Rajeev Krishnan S, Bebawy M . Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis. Trends Pharmacol Sci. 2019; 40(3):172-186. DOI: 10.1016/j.tips.2019.01.006. View

Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S . Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A. 2005; 102(45):16368-73. PMC: 1283450. DOI: 10.1073/pnas.0507904102. View

Du W, Zhang C, Yang W, Yong T, Awan F, Yang B . Identifying and Characterizing circRNA-Protein Interaction. Theranostics. 2017; 7(17):4183-4191. PMC: 5695005. DOI: 10.7150/thno.21299. View

10.

Qiu M, Xia W, Chen R, Wang S, Xu Y, Ma Z . The Circular RNA circPRKCI Promotes Tumor Growth in Lung Adenocarcinoma. Cancer Res. 2018; 78(11):2839-2851. DOI: 10.1158/0008-5472.CAN-17-2808. View

11.

Chaudhuri A, Chabon J, Lovejoy A, Newman A, Stehr H, Azad T . Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. Cancer Discov. 2017; 7(12):1394-1403. PMC: 5895851. DOI: 10.1158/2159-8290.CD-17-0716. View

12.

Li B, Janku F, Jung B, Hou C, Madwani K, Alden R . Ultra-deep next-generation sequencing of plasma cell-free DNA in patients with advanced lung cancers: results from the Actionable Genome Consortium. Ann Oncol. 2019; 30(4):597-603. PMC: 6503621. DOI: 10.1093/annonc/mdz046. View

13.

Wapinski O, Chang H . Long noncoding RNAs and human disease. Trends Cell Biol. 2011; 21(6):354-61. DOI: 10.1016/j.tcb.2011.04.001. View

14.

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

15.

Zhang K, Kang D, Ali M, Liu L, Labanieh L, Lu M . Digital quantification of miRNA directly in plasma using integrated comprehensive droplet digital detection. Lab Chip. 2015; 15(21):4217-26. PMC: 4631652. DOI: 10.1039/c5lc00650c. View

16.

Carthew R . Gene regulation by microRNAs. Curr Opin Genet Dev. 2006; 16(2):203-8. DOI: 10.1016/j.gde.2006.02.012. View

17.

Schwarzenbach H, Nishida N, Calin G, Pantel K . Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014; 11(3):145-56. DOI: 10.1038/nrclinonc.2014.5. View

18.

Yang J, Ahn M, Kim D, Ramalingam S, Sequist L, Su W . Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component. J Clin Oncol. 2017; 35(12):1288-1296. DOI: 10.1200/JCO.2016.70.3223. View

19.

Akhade V, Pal D, Kanduri C . Long Noncoding RNA: Genome Organization and Mechanism of Action. Adv Exp Med Biol. 2017; 1008:47-74. DOI: 10.1007/978-981-10-5203-3_2. View

20.

Danielson K, Rubio R, Abderazzaq F, Das S, Wang Y . High Throughput Sequencing of Extracellular RNA from Human Plasma. PLoS One. 2017; 12(1):e0164644. PMC: 5218574. DOI: 10.1371/journal.pone.0164644. View