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Commercial ctDNA Assays for Minimal Residual Disease Detection of Solid Tumors

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Abstract

The detection of circulating tumor DNA via liquid biopsy has become an important diagnostic test for patients with cancer. While certain commercial liquid biopsy platforms designed to detect circulating tumor DNA have been approved to guide clinical decisions in advanced solid tumors, the clinical utility of these assays for detecting minimal residual disease after curative-intent treatment of nonmetastatic disease is currently limited. Predicting disease response and relapse has considerable potential for increasing the effective implementation of neoadjuvant and adjuvant therapies. As a result, many companies are rapidly investing in the development of liquid biopsy platforms to detect circulating tumor DNA in the minimal residual disease setting. In this review, we discuss the development and clinical implementation of commercial liquid biopsy platforms for circulating tumor DNA minimal residual disease detection of solid tumors. Here, we aim to highlight the technological features that enable highly sensitive detection of tumor-derived genomic alterations, the factors that differentiate these commercial platforms, and the ongoing trials that seek to increase clinical implementation of liquid biopsies using circulating tumor DNA-based minimal residual disease detection.

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Acknowledgements

We are grateful to the National Cancer Institute, the V Foundation for Cancer Research, the Cancer Research Foundation, and Washington University Alvin J. Siteman Cancer Center for funding our work. Images from BioRender.com were used to create Fig. 1.

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Author notes

  1. Kevin Chen and Misty D. Shields contributed equally to this work.

Authors and Affiliations

  1. Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Avenue, St. Louis, MO, 63108, USA

    Kevin Chen, Pradeep S. Chauhan, Peter K. Harris & Aadel A. Chaudhuri

  2. Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Misty D. Shields & Bruna Pellini

  3. Department of Thoracic Oncology, Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Misty D. Shields & Bruna Pellini

  4. Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Ricardo J. Ramirez & Jose P. Zevallos

  5. Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, MO, USA

    Ricardo J. Ramirez, Melissa A. Reimers, Jose P. Zevallos, Andrew A. Davis & Aadel A. Chaudhuri

  6. Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA

    Melissa A. Reimers & Andrew A. Davis

  7. Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

    Aadel A. Chaudhuri

  8. Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA

    Aadel A. Chaudhuri

  9. Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, USA

    Aadel A. Chaudhuri

  10. Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, MO, USA

    Aadel A. Chaudhuri

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  1. Kevin Chen
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Corresponding authors

Correspondence to Andrew A. Davis, Bruna Pellini or Aadel A. Chaudhuri.

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Funding

This work was supported by the NCI under award number K08CA238711 (AAC), the V Foundation for Cancer Research V Scholar Award (AAC), the Cancer Research Foundation Young Investigator Award (AAC), and the Washington University Alvin J. Siteman Cancer Research Fund (AAC). The funders had no role in the preparation of the manuscript.

Conflict of interest

KC, PSC, and RJR have patent filings related to cancer biomarkers. JPZ has patent filings related to cancer biomarkers, research support from Naveris, served as medical director to Summit Biolabs, and has ownership interests in Droplet Biosciences. BP has research support from BMS; speaker honoraria from BioAscend, OncLive, and MJH Life Sciences; and has served as an advisor/consultant to AstraZeneca, Guardant Health, and Guidepoint. AAC has patent filings related to cancer biomarkers, and has served as a consultant/advisor to Roche, Tempus, Geneoscopy, Daiichi Sankyo, AstraZeneca, NuProbe, Fenix Group International, and Guidepoint; AAC has stock options in Geneoscopy, research support from Roche, and ownership interests in Droplet Biosciences. MDS, PKH, MAR, and AAD declare that they have no conflicts of interest that might be relevant to the contents of this review.

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Author contributions

KC, MDS, AAD, BP, and AAC conceived of the study. KC, MDS, PSC, RJR, PKH, AAD, BP, and AAC performed the literature search, data collection, data curation, data interpretation, and writing of the manuscript. All authors edited the manuscript and commented on the manuscript at all stages.

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Chen, K., Shields, M.D., Chauhan, P.S. et al. Commercial ctDNA Assays for Minimal Residual Disease Detection of Solid Tumors. Mol Diagn Ther 25, 757–774 (2021). https://doi.org/10.1007/s40291-021-00559-x

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