Deciphering the Functions of Telomerase Reverse Transcriptase in Head and Neck Cancer

Tsung-Jang Yeh; Chi-Wen Luo; Jeng-Shiun Du; Chien-Tzu Huang; Min-Hung Wang; Tzer-Ming Chuang; Yuh-Ching Gau; Shih-Feng Cho; Yi-Chang Liu; Hui-Hua Hsiao; Li-Tzong Chen; Mei-Ren Pan; Hui-Ching Wang; Sin-Hua Moi

doi:10.3390/biomedicines11030691

Deciphering the Functions of Telomerase Reverse Transcriptase in Head and Neck Cancer

Biomedicines. 2023 Feb 24;11(3):691. doi: 10.3390/biomedicines11030691.

Authors

Tsung-Jang Yeh^{1

2

3}, Chi-Wen Luo^{4

5}, Jeng-Shiun Du^{1

2

3}, Chien-Tzu Huang^{1

2}, Min-Hung Wang^{1

2}, Tzer-Ming Chuang^{1

3}, Yuh-Ching Gau^{1

2

3}, Shih-Feng Cho^{1

2

3}, Yi-Chang Liu^{1

2}, Hui-Hua Hsiao^{1

2}, Li-Tzong Chen^{3

6

7}, Mei-Ren Pan^{2

8

9}, Hui-Ching Wang^{1

2

3}, Sin-Hua Moi²

Affiliations

¹ Division of Hematology & Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
² Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
³ Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁴ Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
⁵ Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan.
⁶ Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁷ National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan.
⁸ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁹ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

Abstract

Head and neck cancers (HNCs) are among the ten leading malignancies worldwide. Despite significant progress in all therapeutic modalities, predictive biomarkers, and targeted therapies for HNCs are limited and the survival rate is unsatisfactory. The importance of telomere maintenance via telomerase reactivation in carcinogenesis has been demonstrated in recent decades. Several mechanisms could activate telomerase reverse transcriptase (TERT), the most common of which is promoter alternation. Two major hotspot TERT promoter mutations (C228T and C250T) have been reported in different malignancies such as melanoma, genitourinary cancers, CNS tumors, hepatocellular carcinoma, thyroid cancers, sarcomas, and HNCs. The frequencies of TERT promoter mutations vary widely across tumors and is quite high in HNCs (11.9-64.7%). These mutations have been reported to be more enriched in oral cavity SCCs and HPV-negative tumors. The association between TERT promoter mutations and poor survival has also been demonstrated. Till now, several therapeutic strategies targeting telomerase have been developed although only a few drugs have been used in clinical trials. Here, we briefly review and summarize our current understanding and evidence of TERT promoter mutations in HNC patients.

Keywords: head and neck cancer; prognosis; promoter mutations; telomerase reverse transcriptase (TERT).

Publication types

Review

Grants and funding

We acknowledge the support from the following grants: (1) KMUH110-0T04 and KMUH111-1M14 from the Kaohsiung Medical University Hospital; (2) 111-2321-B-037 -002 -, 110-2321-B-037-002, 109-2314-B-037-019, 109-2314-B-037-132- and 109-2314-B-037-036-MY3 from the Ministry of Science and Technology, Taiwan; (3) KMU-KI110001, KMU-TC109A03, KMU-TC111A04, KMU-TC108A03-6, and KMU-TC109B05 from Kaohsiung Medical University Research Center Grant.