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J Thorac Oncol. 2019 Mar;14(3):343-357. doi: 10.1016/j.jtho.2018.11.023. Epub 2018 Dec 4.

Biomarkers in Lung Cancer Screening: Achievements, Promises, and Challenges.

Author information

1
Clinica Universidad de Navarra, Madrid, Spain; CIBERES, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.
2
Oncology Division, The Legacy Heritage Oncology Center and Dr. Larry Norton Institute, Soroka Medical Center and Ben-Gurion University, Beer-Sheva, Israel.
3
Solid Tumors Program, Centro de Investigación Médica Aplicada, Pamplona, Spain; Navarra Institute for Health Research, Pamplona, Spain; CIBERONC, Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
4
Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
5
The Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom.
6
Department of Pulmonology, Clinica Universidad de Navarra, Pamplona, Spain; Visiongate Inc., Phoenix, Arizona.
7
Boston University School of Medicine, Boston, Massachusetts.
8
Vanderbilt Ingram Cancer Center, Nashville, Tennessee.
9
Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
10
Solid Tumors Program, Centro de Investigación Médica Aplicada, Pamplona, Spain; Navarra Institute for Health Research, Pamplona, Spain; CIBERONC, Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain; Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, Pamplona, Spain. Electronic address: lmontuenga@unav.es.

Abstract

The present review is an update of the research and development efforts regarding the use of molecular biomarkers in the lung cancer screening setting. The two main unmet clinical needs, namely, the refinement of risk to improve the selection of individuals undergoing screening and the characterization of undetermined nodules found during the computed tomography-based screening process are the object of the biomarkers described in the present review. We first propose some principles to optimize lung cancer biomarker discovery projects. Then, we summarize the discovery and developmental status of currently promising molecular candidates, such as autoantibodies, complement fragments, microRNAs, circulating tumor DNA, DNA methylation, blood protein profiling, or RNA airway or nasal signatures. We also mention other emerging biomarkers or new technologies to follow, such as exhaled breath biomarkers, metabolomics, sputum cell imaging, genetic predisposition studies, and the integration of next-generation sequencing into study of circulating DNA. We also underline the importance of integrating different molecular technologies together with imaging, radiomics, and artificial intelligence. We list a number of completed, ongoing, or planned trials to show the clinical utility of molecular biomarkers. Finally, we comment on future research challenges in the field of biomarkers in the context of lung cancer screening and propose a design of a trial to test the clinical utility of one or several candidate biomarkers.

KEYWORDS:

Biomarkers; Clinical utility; Lung cancer; Screening; Test validation; Trial design

PMID:
30529598
PMCID:
PMC6494979
[Available on 2020-03-01]
DOI:
10.1016/j.jtho.2018.11.023

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