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Review
. 2025 Sep;21(21):2803-2821.
doi: 10.1080/14796694.2025.2542051. Epub 2025 Aug 5.

Recent advances in liquid biopsy for precision oncology: emerging biomarkers and clinical applications in lung cancer

Tancredi Didier Bazan Russo  1 , Francesco Pepe  2 , Valerio Gristina  1 , Andrea Gottardo  1 , Gianluca Russo  2 , Claudia Scimone  2 , Lucia Palumbo  2 , Giulia Busuito  1 , Lorena Incorvaia  1 , Juliette Aimee Guerry  1 , Antonio Galvano  1 , Giuseppe Badalamenti  1 , Viviana Bazan  3 , Giancarlo Troncone  2 , Antonio Russo  1 , Umberto Malapelle  2
Affiliations
Review

Recent advances in liquid biopsy for precision oncology: emerging biomarkers and clinical applications in lung cancer

Tancredi Didier Bazan Russo et al. Future Oncol. 2025 Sep.

Abstract

Lung Cancer (LC) remains the leading cause of cancer-related mortality. While Tissue Biopsy (TB) remains the gold standard for molecular profiling, its invasiveness and inability to provide real-time monitoring have led to the adoption of Liquid Biopsy (LB) as a minimally invasive alternative. By analyzing different circulating analytes such as cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), Circulating Tumor Cells (CTCs), Extracellular Vesicles (EVs), and Tumor-Educated Platelets (TEPs), LB offers a dynamic approach to assessing tumor heterogeneity, Minimal Residual Disease (MRD), and treatment resistance. Recent clinical trials have underscored their role in guiding therapy decisions and monitoring treatment response. In early-stage disease, several Randomized Clinical Trials (RCTs) have shown that ctDNA clearance predicts survival benefits in patients receiving neoadjuvant or perioperative Immune Checkpoint Inhibitors (ICIs). Additionally, adjuvant RCTs have confirmed the ctDNA prognostic role in post-surgical relapse risk assessment. Despite its transformative potential, challenges such as assay standardization, sensitivity limitations in early-stage disease, and regulatory barriers remain. As ongoing research continues to validate its clinical utility, LB is poised to become an indispensable tool in the precision management of LC.

Keywords: MRD; NSCLC; ctDNA; drug resistance; early detection; liquid biopsy; perioperative; precision medicine.

Plain language summary

Lung cancer (LC) is one of the most common and deadly types of cancer worldwide. Traditionally, oncologists have relied on traditional tissue biopsies (TB) for diagnosis and treatment. However, these procedures can be invasive, painful, and sometimes not possible due to the tumor location or patients’ comorbidities. In recent years, a new method called liquid biopsy (LB) has shown great promise. This approach uses a simple and minimally invasive blood test to look for tiny fragments of tumor material – such as DNA, RNA, or small particles – released into the bloodstream. This article reviews how LB is being used in LC care, from helping detect cancer early to monitoring systemic treatments in the clinic. We discuss how certain blood-based markers, especially fragments of tumor DNA (called ctDNA), can signal whether a patient is responding to therapy or if the cancer is relapsing. We also look at new advances in testing technologies and how LB might help physicians personalize treatments for each patient. Despite these advances, there are still challenges. Some patients present with tumors that don’t shed enough DNA into the blood to be detected. The tests themselves can vary in diagnostic accuracy, and there is still work to be done to make them more reliable and widely available. Overall, LB represents an exciting shift toward more personalized and less invasive care for people with LC. As research continues, it may become a routine part of how we diagnose, treat, and monitor this disease in different clinical settings.

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Conflict of interest statement

F.P. received personal fees (as speaker bureau or advisor) from Menarini, Roche unrelated to the current work.

G.T. received personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, all unrelated to the current work.

U.M. received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera, all unrelated to the current work.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

References

    1. Duma N, Santana-Davila R, Molina JR.. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 2019;94(8):1623–1640. doi: 10.1016/j.mayocp.2019.01.013 PubMed PMID: 31378236. - DOI - PubMed
    1. Gristina V, Galvano A, Castellana L, et al. Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses. Ther Adv Med Oncol. 2021;13:17588359211018018. Epub 20210721. doi: 10.1177/17588359211018018 PubMed PMID: 34646363; PubMed Central PMCID: PMC8504650. - DOI - PMC - PubMed
    1. Gottardo A, Gristina V, Perez A, et al. Roles of tumor-educated platelets (TEPs) in the biology of non-small cell lung cancer (NSCLC): a systematic review. “Re-discovering the neglected biosources of the liquid biopsy family”. J Liquid Biopsy. 2024;3:100136. doi: 10.1016/j.jlb.2024.100136 - DOI - PMC - PubMed
    1. Gristina V, Eze C. Editorial: real-world data and real-world evidence in lung cancer. Front Oncol. 2024;14:1436077. Epub 20240607. doi: 10.3389/fonc.2024.1436077 PubMed PMID: 38912056; PubMed Central PMCID: PMC11190332. - DOI - PMC - PubMed
    1. Gristina V, Russo G, Bazan Russo TD, et al. Recent advances in the use of liquid biopsy for the diagnosis and treatment of lung cancer. Expert Rev Respir Med. 2024;18(12):991–1001. Epub 20241103. doi: 10.1080/17476348.2024.2423824 PubMed PMID: 39491533. - DOI - PubMed

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