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The Changing Face of in vitro Culture Models for Thyroid Cancer Research: A Systematic Literature Review

Chew, Dylan; Green, Victoria; Riley, Andrew; England, Richard James; Greenman, John


Dylan Chew

Andrew Riley

Richard James England


© Copyright © 2020 Chew, Green, Riley, England and Greenman. Background: Thyroid cancer is the most common endocrine malignancy worldwide. Primary treatment with surgery and radioactive iodine is usually successful, however, there remains a small proportion of thyroid cancers that are resistant to these treatments, and often represent aggressive forms of the disease. Since the 1950s, in vitro thyroid culture systems have been used in thyroid cancer research. In vitro culture models have evolved from 2-dimensional thyrocyte monolayers into physiologically functional 3-dimensional organoids. Recently, research groups have utilized in vitro thyroid cancer models to identify numerous genetic and epigenetic factors that are involved with tumorigenesis as well as test the efficacy of cytotoxic drugs on thyroid cancer cells and identify cancer stem cells within thyroid tumors. Objective of Review: The objective of this literature review is to summarize how thyroid in vitro culture models have evolved and highlight how in vitro models have been fundamental to thyroid cancer research. Type of Review: Systematic literature review. Search Strategy: The National Institute for Health and Care Excellence (NICE) Healthcare and Databases Advanced Search (HDAS) tool was used to search EMBASE, Medline and PubMed databases. The following terms were included in the search: “in vitro” AND “thyroid cancer”. The search period was confined from January 2008 until June 2019. A manual search of the references of review articles and other key articles was also performed using Google Scholar. Evaluation Method: All experimental studies and review articles that explicitly mentioned the use of in vitro models for thyroid cancer research in the title and/or abstract were considered. Full-text versions of all selected articles were evaluated. Experimental studies were reviewed and grouped according to topic: genetics/epigenetics, drug testing/cancer treatment, and side populations (SP)/tumor microenvironment (TME). Results: Three thousand three hundred and seventy three articles were identified through database and manual searches. One thousand two hundred and sixteen articles remained after duplicates were removed. Five hundred and eighty nine articles were excluded based on title and/or abstract. Of the remaining 627 full-text articles: 24 were review articles, 332 related to genetic/epigenetics, 240 related to drug testing/treatments, and 31 related to SP/TME. Conclusion: In vitro cell culture models have been fundamental in thyroid cancer research. There have been many advances in culture techniques- developing complex cellular architecture that more closely resemble tumors in vivo. Genetic and epigenetic factors that have been identified using in vitro culture models can be used as targets for novel drug therapies. In the future, in vitro systems will facilitate personalized medicine, offering bespoke treatments to patients.


Chew, D., Green, V., Riley, A., England, R. J., & Greenman, J. (2020). The Changing Face of in vitro Culture Models for Thyroid Cancer Research: A Systematic Literature Review. Frontiers in Surgery, 7, Article 43.

Journal Article Type Article
Acceptance Date Jun 8, 2020
Online Publication Date Jul 16, 2020
Publication Date Jul 16, 2020
Deposit Date Jul 16, 2021
Publicly Available Date Oct 27, 2022
Journal Frontiers in Surgery
Electronic ISSN 2296-875X
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 7
Article Number 43
Keywords Thyroid cancer; In vitro; Thyrocyte; Organoids; Epigenetics; Drugs; Cancer stem cells
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Copyright Statement
Copyright © 2020 Chew, Green, Riley, England and Greenman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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