Potential clinical utility of ultrasensitive circulating tumor DNA detection with CAPP-Seq

Abstract

Tumors continually shed DNA into the circulation, where it can be noninvasively accessed. The ability to accurately detect circulating tumor DNA (ctDNA) could significantly impact the management of patients with nearly every cancer type. Quantitation of ctDNA could allow objective response assessment, detection of minimal residual disease and noninvasive tumor genotyping. The latter application overcomes the barriers currently limiting repeated tumor tissue sampling during therapy. Recent technical advancements have improved upon the sensitivity, specificity and feasibility of ctDNA detection and promise to enable innovative clinical applications. Here, we focus on the potential clinical utility of ctDNA analysis using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq), a novel next-generation sequencing-based approach for ultrasensitive ctDNA detection. Applications of CAPP-Seq for the personalization of cancer detection and therapy are discussed.

Keywords:

• biomarker
• circulating tumor DNA
• next-generation sequencing
• noninvasive
• ultrasensitive

Acknowledgements

SV Bratman is supported by a grant from the Radiological Society of North America (RR1221) and has a translational cancer research fellowship with the Association of American Cancer Institutes. M Diehn is supported by a grant from the US National Institutes of Health Director's New Innovator Award Program (1-DP2-CA186596). M Diehn and AA Alizadeh are supported by a grant from the Ludwig Institute for Cancer Research and a grant from the Doris Duke Clinical Scientist Development awards. AM Newman is supported by a grant from the Siebel Stem Cell Institute and the Thomas and Stacey Siebel Foundation.

Financial & competing interests disclosure

SV Bratman, AM Newman, AA Alizadeh, and M Diehn are co-inventors on patent applications related to the CAPP-Seq technology. AA Alizadeh and M Diehn are co-founders and consultants for CAPP Medical. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.