Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC)

Abstract

Globally, non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths. Despite advancements in chemotherapy and targeted therapies, the 5-year survival rate has remained at 16% for the past forty years. Minimal residual disease (MRD) is described as the existence of either isolated tumour cells or circulating tumour cells in biological liquid of patients after removal of the primary tumour without any clinical signs of cancer. Recently, liquid biopsy has been promising as a non-invasive method of disease monitoring and treatment guidelines as an MRD marker. Liquid biopsy could be used to detect and assess earlier stages of NSCLC, post-treatment MRD, resistance to targeted therapies, immune checkpoint inhibitors (ICIs) and tumour mutational burden. MRD surveillance has been proposed as a potential marker for lung cancer relapse. Principally, biosensors provide the quantitative analysis of various materials by converting biological functions into quantifiable signals. Biosensors are usually operated to detect antibodies, enzymes, DNA, RNA, extracellular vesicles (EVs) and whole cells. Here, we present a category of biosensors based on the signal transduction method for identifying biosensor-based biomarkers in liquid biopsy specimens to monitor lung cancer treatment.

Keywords: bio-sensor; liquid biopsy; minimal residual disease; non-small cell lung cancer.

Figure 1

Different stages of lung cancer and clinical application of liquid biopsy. This figure shows the different stages of lung cancer. After surgery, the presence of MRD induces a recurrence. Immunotherapy or target therapy is recommended for treatment and management of relapse. Biosensors are functional for early detection at the screening stage besides identifying new mutants in the advanced cancer stage. Future aspects of biosensors are the assistance of select comprehensive therapy (adjuvant therapy) and monitoring lung cancer at different levels.

Figure 2

Liquid biopsy in lung cancer. Liquid biopsy can be considered for plenty of clinical targets. Liquid biopsy biomarkers are categorised into three main groups: circulating free DNA (cfDNA), CTCs and EVs. cDNA can be used for detecting a wide variety of mutations, such as insertions, deletions and amplification. Capturing and identifying CTCs in whole blood are cooperative for checking proteins and RNA expression and analysing various DNA abnormalities.

Figure 3

Schematic representation of the SPCE electrochemical DNA biosensor to detect lncRNA biomarker MALAT1. Reprinted from ref. [40].