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      Opportunities and Challenges of Liquid Biopsy in Thyroid Cancer

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          Abstract

          Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient’s diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles.

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          Most cited references86

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          Cancer Statistics, 2021

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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            Liquid biopsies come of age: towards implementation of circulating tumour DNA

            Circulating tumour DNA (ctDNA) analysis has the potential to improve prognostication, molecular profiling and disease monitoring in patients with cancer. This Review summarizes recent advances, potential applications in cancer research and personalized oncology, and the introduction of ctDNA into clinical use.
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              Extracellular vesicles in cancer — implications for future improvements in cancer care

              The sustained growth, invasion, and metastasis of cancer cells depend upon bidirectional cell-cell communication within complex tissue environments. Such communication predominantly involves the secretion of soluble factors by cancer cells and/or stromal cells within the tumour microenvironment (TME), although these cell types have also been shown to export membrane-encapsulated particles containing regulatory molecules that contribute to cell-cell communication. These particles are known as extracellular vesicles (EVs) and include species of exosomes and shed microvesicles. EVs carry molecules such as oncoproteins and oncopeptides, RNA species (for example, microRNAs, mRNAs, and long non-coding RNAs), lipids, and DNA fragments from donor to recipient cells, initiating profound phenotypic changes in the TME. Emerging evidence suggests that EVs have crucial roles in cancer development, including pre-metastatic niche formation and metastasis. Cancer cells are now recognized to secrete more EVs than their nonmalignant counterparts, and these particles can be isolated from bodily fluids. Thus, EVs have strong potential as blood-based or urine-based biomarkers for the diagnosis, prognostication, and surveillance of cancer. In this Review, we discuss the biophysical properties and physiological functions of EVs, particularly their pro-metastatic effects, and highlight the utility of EVs for the development of cancer diagnostics and therapeutics.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                19 July 2021
                July 2021
                : 22
                : 14
                : 7707
                Affiliations
                [1 ]Center of Experimental Oncology and Hematology, A.O.U. Policlinico “G. Rodolico—San Marco”, 95123 Catania, Italy; chiararomano83@ 123456gmail.com (C.R.); federica.martorana@ 123456phd.unict.it (F.M.); perny76@ 123456gmail.com (M.S.P.); stefania.stel@ 123456gmail.com (S.S.); michedot@ 123456yahoo.it (M.M.); elena.tirro@ 123456unipa.it (E.T.); silviarita.vitale@ 123456gmail.com (S.R.V.); digregoriosandra@ 123456hotmail.com (S.D.G.); adry.p88@ 123456hotmail.it (A.P.); cristina.tomarchio@ 123456hotmail.it (C.T.)
                [2 ]Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
                [3 ]Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, 90127 Palermo, Italy
                Author notes
                [* ]Correspondence: manzella@ 123456unict.it ; Tel.: +39-095-3781970
                [†]

                C.R. and F.M. equally contributed to this work.

                Author information
                https://orcid.org/0000-0002-2586-8266
                https://orcid.org/0000-0002-7189-2312
                https://orcid.org/0000-0001-5896-8573
                https://orcid.org/0000-0001-8012-5134
                Article
                ijms-22-07707
                10.3390/ijms22147707
                8303548
                34299334
                d70a4a60-6ac0-48a7-8a34-4e7904044b6f
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 22 June 2021
                : 12 July 2021
                Categories
                Review

                Molecular biology
                differentiated thyroid cancer,anaplastic thyroid cancer,medullary thyroid cancer,liquid biopsy,diagnosis,prognosis,therapy

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