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Lee et al. J Cancer Metastasis Treat 2021;7:27 Journal of Cancer
DOI: 10.20517/2394-4722.2021.58
Metastasis and Treatment

Review Open Access

Targeting transcriptional regulators for treatment of
anaplastic thyroid cancer

Woo Kyung Lee, Sheue-Yann Cheng

Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda,
MD 20892, USA.
Correspondence to: Dr. Sheue-Yann Cheng, Chief, Gene Regulation Section, Laboratory of Molecular Biology, National Cancer
Institute, National Institutes of Health, 37 Convent Dr, Room 5128, Bethesda, MD 20892-4264, USA. E-mail:
chengs@mail.nih.gov

How to cite this article: Lee WK, Cheng SY. Targeting transcriptional regulators for treatment of anaplastic thyroid cancer. J
Cancer Metastasis Treat 2021;7:27. https://dx.doi.org/10.20517/2394-4722.2021.58

Received: 10 Mar 2021 First Decision: 19 Apr 2021 Revised: 28 Apr 2021 Accepted: 8 May 2021 Published: 25 May 2021

Academic Editors: Jerome M. Hershman, Lucio Miele Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Dysregulation of genes perpetuates cancer progression. During carcinogenesis, cancer cells acquire dependency of
aberrant transcriptional programs (known as “transcription addiction”) to meet the high demands for uncontrolled
proliferation. The needs for particular transcription programs for cancer growth could be cancer-type-selective.
The dependencies of certain transcription regulators could be exploited for therapeutic benefits. Anaplastic thyroid
cancer (ATC) is an extremely aggressive human cancer for which new treatment modalities are urgently needed.
Its resistance to conventional treatments and the lack of therapeutic options for improving survival might have
been attributed to extensive genetic heterogeneity due to subsequent evolving genetic alterations and clonal
selections during carcinogenesis. Despite this genetic complexity, mounting evidence has revealed a characteristic
transcriptional addiction of ATC cells resulting in evolving diverse oncogenic signaling for cancer cell survival. The
transcriptional addiction has presented a huge challenge for effective targeting as shown by the failure of previous
targeted therapies. However, an emerging notion is that many different oncogenic signaling pathways activated by
multiple upstream driver mutations might ultimately converge on the transcriptional responses, which would
provide an opportunity to target transcriptional regulators for treatment of ATC. Here, we review the current
understanding of how genetic alterations in cancer distorted the transcription program, leading to acquisition of
transcriptional addiction. We also highlight recent findings from studies aiming to exploit the opportunity for
targeting transcription regulators as potential therapeutics for ATC.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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