Current and future applications of liquid biopsy in non-small-cell lung cancer—a narrative review

Abstract

Background and Objective Lung cancer remains the leading cause of cancer-related mortality and constitutes a significant societal burden. Recent advancements in targeted therapies and immunotherapy have considerably broadened therapeutic options in lung cancer, particularly in non-small-cell lung cancer (NSCLC). However, these novel methods necessitate sophisticated molecular diagnostics. Liquid biopsy, which refers to the cytological and molecular analysis of cancer markers shed by the tumor into the body fluids, may offer an attractive diagnostic tool at the individual patient level. This approach is particularly relevant for lung cancer, as the anatomical location of tumor lesions frequently makes them inaccessible for tissue biopsy. Apart from minimal invasiveness, the major advantages of liquid biopsy include better reflection of the tumor clonal heterogeneity (spatial heterogeneity), the possibility of sequential sampling, and real-time monitoring of tumor load and its evolving mutational status (temporal heterogeneity). Methods This article reviews the available data in this field, current applications, and future perspectives in accordance with the Narrative Review reporting rules. Key Content and Findings We discuss the most used approaches, i.e., circulating DNA and tumor cells, but also emerging liquid biopsy techniques, such as plasma DNA methylation, plasma metabolites and RNA, extracellular vesicles, and tumor-educated platelets in NSCLC. Finally, we highlight the current limitations of liquid biopsy techniques hampering their clinical applications. Conclusions Due to their advantages, liquid biopsy-based approaches have recently gained immense interest in oncology. Potential applications of this method include early detection, informing precision medicine-based individualized treatment, and real-time monitoring of disease evolution and treatment. The development of next-generation sequencing has vastly extended genetic profiling, thus enabling better identification of druggable alterations. However, the clinical application of liquid biopsy techniques is still limited due to their suboptimal specificity and sensitivity, lack of standardization, and relatively high costs. Addressing these issues may allow further integration of liquid biopsies in the routine clinical setting, thus making a profound and permanent change in NSCLC management.

Robust diagnosis of infectious disease, autoimmunity and cancer from the paratope networks of adaptive immune receptors

“…Non-small cell lung cancer (NSCLC) is the most common type of lung cancer; it consist primarily of squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, but several rarer subtypes have also been identified 33 . Diagnosis traditionally relies upon a wide variety of evidence, including symptoms (e.g., persistent cough), imaging data, and tissue biopsy; however, diagnoses based on blood-based biomarkers ( EGFR, HER2, BRAF, KRAS, MET etc ) 34 have recently become more common in the application of liquid biopsy in NSCLC 35 . Like in many other cancers, in NSCLC, disease-specific T cells often infiltrate tumors, but whether these T cells also circulate in the blood remains poorly understood.…”

Liquid Biopsy in Lung Cancer: Biomarkers for the Management of Recurrence and Metastasis

“…In the context of ITH, liquid biopsies offer a range of potential applications, including early detection, the detection of MRD, the guidance of treatment decisions, the investigation of treatment efficacy and resistance, and real-time disease monitoring [40,155].…”

“…As technology continues to evolve, liquid biopsies are slowly becoming indispensable for the clinical management of advanced lung cancer. Although previous studies have investigated liquid biopsies in lung cancer [38][39][40][41][42], our review offers novel insights by specifically highlighting their potential applications for the management of metastasis and recurrence in NSCLC. Here, we comprehensively review relevant data, contributing to the literature by thoroughly elucidating the role of liquid biopsies with a focus on clinical applications for the better management of metastatic and recurrent NSCLC, which are the most serious and poorly managed clinical complications of lung cancer leading to treatment failure and patient death.…”

Identification and validation of PCDHGA12 and PRRX1 methylation for detecting lung cancer in bronchial washing sample

“…Lung cancer (LC) is the leading cause of cancer-related mortality and morbidity, with 1.8 million deaths accounting for 18% of the global cancer-associated mortality rate ( 1 , 2 ). The estimated 5-year survival rate of patients with LC is 68–92% when diagnosed at an early stage.…”