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Review
. 2020 Mar:207:107458.
doi: 10.1016/j.pharmthera.2019.107458. Epub 2019 Dec 18.

Circulating tumor DNA as an early cancer detection tool

Andrea Campos-Carrillo  1 , Jeffrey N Weitzel  1 , Prativa Sahoo  1 , Russell Rockne  1 , Janet V Mokhnatkin  1 , Muhammed Murtaza  2 , Stacy W Gray  1 , Laura Goetz  3 , Ajay Goel  1 , Nicholas Schork  3 , Thomas P Slavin  4
Affiliations
Review

Circulating tumor DNA as an early cancer detection tool

Andrea Campos-Carrillo et al. Pharmacol Ther. 2020 Mar.

Abstract

Circulating tumor DNA holds substantial promise as an early detection biomarker, particularly for cancers that do not have currently accepted screening methodologies, such as ovarian, pancreatic, and gastric cancers. Many features intrinsic to ctDNA analysis may be leveraged to enhance its use as an early cancer detection biomarker: including ctDNA fragment lengths, DNA copy number variations, and associated patient phenotypic information. Furthermore, ctDNA testing may be synergistically used with other multi-omic biomarkers to enhance early detection. For instance, assays may incorporate early detection proteins (i.e., CA-125), epigenetic markers, circulating tumor RNA, nucleosomes, exosomes, and associated immune markers. Many companies are currently competing to develop a marketable early cancer detection test that leverages ctDNA. Although some hurdles (like early stage disease assay accuracy, high implementation costs, confounding from clonal hematopoiesis, and lack of clinical utility studies) need to be addressed before integration into healthcare, ctDNA assays hold substantial potential as an early cancer screening test.

Keywords: Cancer detection; Cancer screening; Cell-free DNA; Circulating tumor DNA; Early detection.

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Conflict of interest statement

Declaration of Competing Interest MM is an inventor on patent applications covering technologies described herein. SWG is a consultant to Grail, Inc. Laura Goetz holds an equity position in Q Bio, Inc. All other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Synergistic inclusion of both intrinsic variables with multi-omic technologies may enhance circulating tumor DNA as a tool for early cancer detection. A patient with an undiagnosed lung cancer is shown. Phenotypic variables in this case could include age and smoking status to help inform the prior probability of lung adenocarcinoma.
See this image and copyright information in PMC

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