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Telomerase and Telomeres Biology in Thyroid Cancer

Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
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Int. J. Mol. Sci. 2019, 20(12), 2887; https://doi.org/10.3390/ijms20122887
Received: 30 April 2019 / Revised: 3 June 2019 / Accepted: 11 June 2019 / Published: 13 June 2019
(This article belongs to the Special Issue Role of Telomeres and Telomerase in Cancer and Aging 2019)
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Abstract

Telomere and telomerase regulation contributes to the onset and evolution of several tumors, including highly aggressive thyroid cancers (TCs). TCs are the most common endocrine malignancies and are generally characterized by a high rate of curability. However, a small but significant percentage develops distant metastasis or progresses into undifferentiated forms associated with bad prognosis and for which poor therapeutic options are available. Mutations in telomerase reverse transcriptase (TERT) promoter are among the most credited prognostic marker of aggressiveness in TCs. Indeed, their frequency progressively increases passing from indolent lesions to aggressive and anaplastic forms. TERT promoter mutations create binding sites for transcription factors, increasing TERT expression and telomerase activity. Furthermore, aggressiveness of TCs is associated with TERT locus amplification. These data encourage investigating telomerase regulating pathways as relevant drivers of TC development and progression to foster the identification of new therapeutics targets. Here, we summarize the current knowledge about telomere regulation and TCs, exploring both canonical and less conventional pathways. We discuss the possible role of telomere homeostasis in mediating response to cancer therapies and the possibility of using epigenetic drugs to re-evaluate the use of telomerase inhibitors. Combined treatments could be of support to currently used therapies still presenting weaknesses. View Full-Text
Keywords: telomeres; telomerase; thyroid cancer; TERT promoter; EMT; BRD4; epigenetic drugs; combined therapies telomeres; telomerase; thyroid cancer; TERT promoter; EMT; BRD4; epigenetic drugs; combined therapies
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Donati, B.; Ciarrocchi, A. Telomerase and Telomeres Biology in Thyroid Cancer. Int. J. Mol. Sci. 2019, 20, 2887.

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