Ann Lab Med.  2018 Jan;38(1):1-8. 10.3343/alm.2018.38.1.1.

Cell-Free DNA in Oncology: Gearing up for Clinic

• Ulrich BC
• Paweletz C

• KMID: 2397595
• DOI: http://doi.org/10.3343/alm.2018.38.1.1

Abstract

In the past several years, interest in the clinical utility of cell-free DNA as a noninvasive cancer biomarker has grown rapidly. Success in the development of plasma genotyping assays and other liquid biopsy assays has widened the scope of cell-free DNA use in research and the clinic. Already approved by the US Food and Drug Administration in the narrow context of epidermal growth factor receptor-mutated non-small cell lung cancer, plasma genotyping assays are currently being investigated in a wide array of clinical settings and modalities. These include plasma genotyping as a tool for early diagnosis, the detection of minimal residual disease, and the evaluation of treatment response/progression. In this review, we assess the clinical landscape of plasma genotyping assays and propose strategies for their further expansion into routine clinical care.

Keyword

Liquid biopsy; Cell-free DNA; Plasma genotyping; Non-invasive biomarkers; Clinical trials

MeSH Terms

Biopsy
Carcinoma, Non-Small-Cell Lung
DNA*
Early Diagnosis
Epidermal Growth Factor
Neoplasm, Residual
Plasma
United States Food and Drug Administration
DNA
Epidermal Growth Factor

Figure

• 

  Fig. 1 Plasma genotyping assays can use cell-free DNA to longitudinally track dynamic cancer responses in diverse clinical situations. In particular, these assays can evaluate responses to targeted agents and the presence or recurrence of disease after curative surgery.

• 

  Fig. 2 The clinical trial landscape for cell-free DNA. (A) Three major clinical trial types conducted in the field of cell-free DNA analysis. Concordance trials assess the accuracy of plasma genotyping assays to capture genetic mutations found in tumor tissue. Observational trials explore the predictive capacity of cell-free DNA as a biomarker. Interventional trials compare treatment outcomes of clinical decision-making with plasma genotyping versus standard of care (imaging, tissue biopsy, etc.). (B) Graph of clinical trials registered to clinicaltrials.gov that have investigated some aspect of plasma genotyping in oncology. This highlights the rapid growth of interest in the clinical utility of cell-free DNA and the recent initiation of interventional trials.

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