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.

Electroanalytical overview: screen-printed electrochemical sensing platforms for the detection of vital cardiac, cancer and inflammatory biomarkers

“…[99][100][101] From a monitoring perspective, they allow for easy and frequent repeated testing and have been shown to be extremely useful for detection of minimal residual disease and risk of relapse. 102,103 The advent of 'personalised medicine' in which a patient's treatment is tailored towards their specific genetic or molecular profile has certainly been a key driver of the push for biomarker validation. Indeed, there are numerous examples of cancer biomarkers that are used to quantify the residual risk faced by patients and identify those groups of patients likely to benefit from costly, novel treatment approaches.…”

Application of Non-Blood-Derived Fluid Biopsy in Monitoring Minimal Residual Diseases of Lung Cancer

“…With the progress of technology, the sensitivity of personalized gene sequencing technologies in tracking more mutations and thereby detecting low-volume MRD is gradually increasing. However, the clinical application of liquid biopsy is limited due to its operating cost ( 11 ). The obvious advantage of some non-blood-derived fluid biopsies is that the exfoliated tumor cells can be collected from the body fluids in direct contact with the tumor, ensuring the content of tumor markers and their correlation with the primary tumor.…”

Investigate the application of postoperative ctDNA-based molecular residual disease detection in monitoring tumor recurrence in patients with non-small cell lung cancer——A retrospective study of ctDNA

“…In recent years, liquid biopsy has been introduced into clinical practice as a valuable tool for early diagnosis of recurrence and metastasis of non-small cell lung cancer (NSCLC) (8)(9)(10)(11)(12). Circulating tumor DNA (ctDNA) mainly comes from the small fragments of DNA released by apoptotic or necrotic tumor cells in tumor tissues into the blood system and the DNA released by the lysis of circulating tumor cells or micrometastases in the blood (13).…”

“…It has been widely used for early diagnosis, prognostic stratification, disease monitoring and treatment response assessment in different cancer types ( 14 – 16 ). Liquid biopsy techniques based on plasma ctDNA analysis can monitor and track personalized disease-related markers at the molecular level, and can be used to detect molecular residual desease (MRD) after treatment ( 10 , 17 , 18 ). In the TRACERx study, Addosh et al ( 19 ) found that ctDNA test after surgery could detect tumor recurrence or metastasis earlier than imaging.…”