Review Article
Biomarkers in Lung Cancer Screening: Achievements, Promises, and Challenges

https://doi.org/10.1016/j.jtho.2018.11.023Get rights and content
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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
Lung cancer
Screening
Test validation
Clinical utility
Trial design

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Disclosure: Dr. Peled is an advisor for and has received honoraria from AstraZemeca, Bohringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, NovellusDx, Foundation Medicine, Inc., and Gaurdant360; in addition, he is a coinventor in breath analysis in lung cancer. Dr. Ajona, Dr. Pio, and Dr. Montuenga are listed as coinventors of two patents related to the use of complement fragments as biomarkers. Dr. Sozzi and Dr. Boeri are coinventors of three patent applications regarding the microRNA signature MSC. These patents were licensed to a private company, Gensignia Life Science, under regulations of Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. Dr. Zulueta is an employee and shareholder of VisionGate, Inc. Dr. Spira is an employee of Johnson and Johnson and has provided prior consultant to Veracyte, Inc. Dr. Mazzone has participated in advisory board discussions for Exact Sciences, SeerPharma, and Grail in the past 12 months. Dr. Seijo has received professional fees for speaking engagements regarding lung cancer screening and received an unrestricted grant from Menarini in support of the Jimenez Díaz Foundation’s lung cancer screening program. The remaining authors declare no conflict of interest.