Minimally invasive biomarkers for triaging lung nodules—challenges and future perspectives

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Afridi, Waqar Ahmed
Picos, Samandra Hernandez
Bark, Juliana Muller
Stamoudis, Danyelle Assis Ferreira
Vasani, Sarju
Irwin, Darryl
Fielding, David
Punyadeera, Chamindie
Griffith University Author(s)
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2025
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Abstract

CT chest scans are commonly performed worldwide, either in routine clinical practice for a wide range of indications or as part of lung cancer screening programs. Many of these scans detect lung nodules, which are small, rounded opacities measuring 8-30 mm. While the concern about nodules is that they may represent early lung cancer, in screening programs, only 1% of such nodules turn out to be cancer. This leads to a series of complex decisions and, at times, unnecessary biopsies for nodules that are ultimately determined to be benign. Additionally, patients may be anxious about the status of detected lung nodules. The high rate of false positive lung nodule detections has driven advancements in biomarker-based research aimed at triaging lung nodules (benign versus malignant) to identify truly malignant nodules better. Biomarkers found in biofluids and breath hold promise owing to their minimally invasive sampling methods, ease of use, and cost-effectiveness. Although several biomarkers have demonstrated clinical utility, their sensitivity and specificity are still relatively low. Combining multiple biomarkers could enhance the characterisation of small pulmonary nodules by addressing the limitations of individual biomarkers. This approach may help reduce unnecessary invasive procedures and accelerate diagnosis in the future. This review offers a thorough overview of emerging minimally invasive biomarkers for triaging lung nodules, emphasising key challenges and proposing potential solutions for biomarker-based nodule differentiation. It focuses on diagnosis rather than screening, analysing research published primarily in the past five years with some exceptions. The incorporation of biomarkers into clinical practice will facilitate the early detection of malignant nodules, leading to timely interventions and improved outcomes. Further efforts are needed to increase the cost-effectiveness and practicality of many of these applications in clinical settings. However, the range of technologies is advancing rapidly, and they may soon be implemented in clinics in the near future.

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Cancer and Metastasis Reviews

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44

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1

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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Oncology and carcinogenesis

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Afridi, WA; Picos, SH; Bark, JM; Stamoudis, DAF; Vasani, S; Irwin, D; Fielding, D; Punyadeera, C, Minimally invasive biomarkers for triaging lung nodules-challenges and future perspectives, Cancer and Metastasis Reviews, 2025, 44 (1), pp. 29

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