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Review
. 2023 Sep;11(9):e006013.
doi: 10.1136/jitc-2022-006013.

Cell-free DNA approaches for cancer early detection and interception

Jamie E Medina  1 , Nicholas C Dracopoli  2 , Peter B Bach  2 , Anna Lau  2 , Robert B Scharpf  1 , Gerrit A Meijer  3 , Claus Lindbjerg Andersen  4 , Victor E Velculescu  5
Affiliations
Review

Cell-free DNA approaches for cancer early detection and interception

Jamie E Medina et al. J Immunother Cancer. 2023 Sep.

Abstract

Rapid advancements in the area of early cancer detection have brought us closer to achieving the goals of finding cancer early enough to treat or cure it, while avoiding harms of overdiagnosis. We evaluate progress in the development of early cancer detection tests in the context of the current principles for cancer screening. We review cell-free DNA (cfDNA)-based approaches using mutations, methylation, or fragmentomes for early cancer detection. Lastly, we discuss the challenges in demonstrating clinical utility of these tests before integration into routine clinical care.

Keywords: Biomarkers, Tumor; Neoplastic Cells, Circulating; Review.

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Conflict of interest statement

Competing interests: The authors declare the following competing interests: NCD, PBB, and AL report that they are employees of and have stock ownership in Delfi Diagnostics. RBS reports grants and personal fees from Delfi Diagnostics outside the submitted work; a patent for US-2022-0325343 licensed to Delfi Diagnostics; and is a founder of and holds equity in Delfi Diagnostics, and serves as the head of Data Science. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. GAM reports that his institution has received grants from SU2C-Dutch Cancer Society (KWF), Sysmex in-kind matching to KWF grant, MLDS and Health~Holland with in-kind matching from Exact Sciences, ZonMW with in-kind matching from HMF and Personal Genome Diagnostics (PGDx) and cash matching from CZ Health Insurance paid to the institution. GAM is named as a co-inventor on a patent issued for protein biomarkers for detection of colorectal cancer and patents pending related to biomarkers for colorectal cancer early detection and related cell-free DNA analyses. GAM is a participant in the Amgen Real-World Data group, for which he receives no compensation. GAM is a Board member and CSO of Health-RI, a Supervisory Board member of IKNL, a Co-national Node Leader of BBMRI-NL, and a National Node Director of EATRIS-NL. GAM is a co-founder, Board member, and CSO of CRCbioscreen BV. GAM reports research collaborations with Exact Sciences, Sysmex, Sentinel Ch. SpA, PGDx, Hartwig Medical Foundation, and Delfi Diagnostics, in which the companies have provided materials, equipment, and/or analyses. CLA reports that his institution has received grants or contracts from C2i Genomics, Delfi Diagnostics, and Natera. VEV is a founder of Delfi Diagnostics, serves on the Board of Directors and as an officer for this organization, and owns Delfi Diagnostics stock, which is subject to certain restrictions under university policy. Additionally, Johns Hopkins University owns equity in Delfi Diagnostics. VEV divested his equity in Personal Genome Diagnostics (PGDx) to LabCorp in February 2022. VEV is an inventor on patent applications submitted by Johns Hopkins University related to cancer genomic analyses and cell-free DNA for cancer detection that have been licensed to one or more entities, including Delfi Diagnostics, LabCorp, QIAGEN, Sysmex, Agios, Genzyme, Esoterix, Ventana and ManaT Bio. Under the terms of these license agreements, the University and inventors are entitled to fees and royalty distributions. VEV is an advisor to Viron Therapeutics and Epitope. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies.

Figures

Figure 1
Figure 1. Liquid biopsy approaches for cancer detection. Cell-free DNA technologies evaluating mutations or methylation are often costly, multistep, time consuming processes prior to data analyses. Low-coverage whole-genome sequencing approaches can minimize arduous laboratory protocols at low-cost with broadly applicable bioinformatic pipelines. cfDNA, cell-free DNA; MAF, mutant allele frequency.
See this image and copyright information in PMC

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