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Review
. 2018 Jun;97(6):701-708.
doi: 10.1177/0022034518762071. Epub 2018 Mar 7.

Liquid Biopsy in Head and Neck Cancer: Promises and Challenges

T Nonaka  1   2 , D T W Wong  1   2
Affiliations
Review

Liquid Biopsy in Head and Neck Cancer: Promises and Challenges

T Nonaka et al. J Dent Res. 2018 Jun.

Abstract

Head and neck cancer is the sixth most common cancer worldwide. It remains one of the leading causes of death, and its early detection is crucial. Liquid biopsy has emerged as a promising tool for detecting and monitoring the disease status of patients with early and advanced cancers. Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal miRNAs have received enormous attention because of their apparent clinical implications. Analyses of these circulating biomarkers have paved the way for novel therapeutic approaches and precision medicine. A growing number of reports have implicated the use of circulating biomarkers for detection, treatment planning, response monitoring, and prognosis assessment. Although these new biomarkers can provide a wide range of possible clinical applications, no validated circulating biomarkers have yet been integrated into clinical practice for head and neck cancer. In this review, we summarize the current knowledge of circulating biomarkers in this field, focusing on their feasibility, limitations, and key areas of clinical applications. We also highlight recent advances in salivary diagnostics and their potential application in head and neck cancer.

Keywords: biomarker; circulating tumor DNA; circulating tumor cell; exosomal miRNA; saliva-exosomics; salivary diagnostics.

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Conflict of interest statement

D.T.W. Wong is the cofounder of RNAmeTRIX, a molecular diagnostic company. D.T.W. Wong holds equity in RNAmeTRIX and serves as a company director and scientific advisor. The University of California also holds equity in RNAmeTRIX. Intellectual property that D.T.W. Wong invented and that was patented by the University of California has been licensed to RNAmeTRIX. D.T.W. Wong is a consultant to GlaxoSmithKlein, Wrigley, and Colgate-Palmolive. The authors declare no other potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
Circulating biomarkers in head and neck cancer. Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal miRNAs are complementary biomarkers present in plasma and/or saliva. Apoptotic tumor cells release ctDNA into blood, whereas necrotic tumor cells shed ctDNA into saliva. Tumor cells release exosomal miRNAs into blood and saliva. Primary tumor and metastatic lesions release CTCs into blood.
Figure 2.
Figure 2.
Potential clinical applications of circulating biomarkers in the treatment of head and neck cancer. (A) Schematic time course of disease management and tumor size in head and neck cancer patients undergoing chemotherapy (or immunotherapy) and surgery. Plasma circulating tumor DNA (ctDNA) analysis allows early detection, monitoring treatment response, monitoring minimal residual disease (MRD), and predicting metastasis. Circulating tumor cell (CTC) analysis can assist the selection of targeted therapies. Exosomal miRNAs currently offer limited insight into clinical applications. Salivary ctDNA analysis can provide complementary information. (B) Use of plasma and salivary ctDNA in combination allows higher detection of cancer than use of plasma ctDNA alone. A spike in ctDNA level reflects transient tumor cell death by systemic therapy.
See this image and copyright information in PMC

References

    1. Alix-Panabières C, Pantel K. 2016. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 6(5):479–491. - PubMed
    1. Beaver JA, Jelovac D, Balukrishna S, Cochran R, Croessmann S, Zabransky DJ, Wong HY, Toro PV, Cidado J, Blair BG, et al. 2014. Detection of cancer DNA in plasma of patients with early-stage breast cancer. Clin Cancer Res. 20(10):2643–2650. - PMC - PubMed
    1. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, et al. 2014. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 6(224):224ra24. - PMC - PubMed
    1. Buglione M, Grisanti S, Almici C, Mangoni M, Polli C, Consoli F, Verardi R, Costa L, Paiar F, Pasinetti N, et al. 2012. Circulating tumour cells in locally advanced head and neck cancer: preliminary report about their possible role in predicting response to non-surgical treatment and survival. Eur J Cancer. 48(16):3019–3026. - PubMed
    1. Butt AQ, Mills KH. 2014. Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines. Oncogene. 33(38):4623–4631. - PubMed

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