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Review
. 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

Luis M Seijo  1 , Nir Peled  2 , Daniel Ajona  3 , Mattia Boeri  4 , John K Field  5 , Gabriella Sozzi  4 , Ruben Pio  3 , Javier J Zulueta  6 , Avrum Spira  7 , Pierre P Massion  8 , Peter J Mazzone  9 , Luis M Montuenga  10
Affiliations
Review

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

Luis M Seijo et al. J Thorac Oncol. 2019 Mar.

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.

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Conflict of interest statement

Conflicts of interest:

NP is advisor for and received honoraria from AZ, BI, BMS, Lilly, MSD, Novartis, Pfizer, Roche, NovellusDx, FMI, Gaurdant360 and is a co-inventor in breath analysis in lung cancer. DA, RP and LMM are listed as co-inventors of two patents related to the use of complement fragments as biomarkers. G.S and M.B. are co-inventors for three patent applications regarding the miRNA signature MSC. These patents were licensed to a private company, Gensignia Life Science, under regulations of Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. JJZ is an employee and shareholder of VisionGate, Inc. AS is an employee of JNJ and prior consultant to Veracyte Inc. PJM has participated in the past 12 months in advisory board discussions for Exact Sciences, SEER, and Grail. LMS has received professional fees for speaking engagements regarding lung cancer screening and received an unrestricted grant from Menarini in support of the Fundación Jimenez Díaz’s lung cancer screening program.

Figures

Figure 1.
Figure 1.
Criteria for clinical use of biomarkers.
Figure 2.
Figure 2.
Currently explored biomarker candidates. miRNA, microRNA.
Figure 3:
Figure 3:
Candidate biomarkers for lung cancer early detection and phase of development RMS: risk management in screening context; DIPN: diagnosis of indeterminate pulmonary nodules; *DECAMP-1 and DECAMP-2 trials (NCT01785342 and NCT02504697) are currently recruiting patients in order to test some of these biomarkersAAB Autoantibody.
Figure 4.
Figure 4.
Design of a trial to test the clinical utility of one or several candidate biomarkers. CT, computed tomography; LDCT, low-dose computed tomography; SOC, standard of care; USPSTF, U.S. Preventive Services Task Force; PRO, patient-reported outcomes.
See this image and copyright information in PMC

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