Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review

Simple Summary Lung cancer remains a leading cause of cancer-related mortality globally, requiring new diagnostic and therapeutic approaches. This research arises from the need to improve diagnostic accuracy and treatment effectiveness for patients with non-small cell lung cancer. The authors aim to systematically evaluate the potential of emerging biomarkers, including circulating tumor DNA, microRNAs and mutational load of blood tumors and their relationship with different treatments. The findings of this study could have a significant impact on the research community by providing a basis for integrating these biomarkers into clinical practice, thereby improving personalized treatment strategies and patient outcomes in non-small cell lung cancer.Abstract Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers-circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood tumor mutational burden (bTMB)-enhanced by next-generation sequencing (NGS) to improve the diagnostic accuracy, prognostic evaluation, and treatment strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients from 2020 to 2024, the review highlights how biomarkers like ctDNA and PD-L1 expression critically inform the selection of personalized therapies, particularly beneficial in the advanced stages of NSCLC. These biomarkers are critical for prognostic assessments and in dynamically adapting treatment plans, where high PD-L1 expression and specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide the use of targeted therapies and immunotherapies. The findings recommend integrating these biomarkers into standardized clinical pathways to maximize their potential in enhancing the treatment precision, ultimately fostering significant advancements in oncology and improving patient outcomes and quality of life. This review substantiates the prognostic and predictive value of these biomarkers and emphasizes the need for ongoing innovation in biomarker research.