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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 22278

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Dr. Vui King Vincent-Chong

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Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
Interests: oral oncology
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Oral cancer is a commonly occurring head and neck cancer, 90% of cases of which are diagnosed as oral squamous cell carcinoma (OSCC). This lethal malignancy is a debilitating disease that impacts patients’ physical appearance, causing disfiguration and devastating their self-esteem. Despite improvements in diagnostic facilities and patient management, the prognosis of OSCC remains poor.

Histologically, OSCC is derived from a multistep mechanism known as oral carcinogenesis, which progresses from normal epithelium to hyperplasia, followed by dysplasia and carcinoma in situ and precedes the development of invasive squamous cell carcinoma. Caused by exposure to carcinogens, such as smoking and excessive alcohol drinking and HPV infections, this multistep mechanism is characterized by mutations related to copy number alteration and epigenetic modifications.

Precision medicine based on genomic profiling is also becoming more prevalent. It relies on the genetic information of individual patients or specific cancer cells and how their genes interact with each other and the environment. This method has the potential to provide more effective treatment strategies as approaches can be customized for the specific genetic profiles of patients. The completion of the TCGA HNSCC database has led to the development of new therapeutic approaches and targeted therapies. Lately, immune checkpoint inhibitors have been recognized as one of the standards of care in HNSCC. However, although treating invasive SCC is crucial, the implementation of prevention strategies to preclude malignant transformation has been useful in clinical management.

Topics of interest for this Special Issue include, but are not limited to:

Precision medicine, i.e., targeted therapies that inhibit oral carcinogenesis and tumorigenesis mechanisms;
Combination of novel therapeutic approaches with standard-of-care regimens in OSCC;
Biomarkers, i.e., predictive and prognostic markers for therapeutic approaches.

For this Special Issue of Biomedicines, entitled “Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches,” we are inviting the submission of original articles, review articles, systematic reviews, and meta-analyses considering oral carcinogenesis, tumorigenesis, and novel therapeutic approaches as well as biomarkers for treatment efficacy. New experimental clinical results for HNSCC are also welcome.

I look forward to receiving your contributions.

Dr. Vui King Vincent-Chong
Guest Editor

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Keywords

oral carcinogenesis
oral tumorigenesis
OSCC
ICI
mutation
biomarkers
chemoradiation
targeted therapies
cisplatin
preclinical models

Related Special Issue

Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches Volume II in Biomedicines (1 article)

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Editorial

Jump to: Research, Review

5 pages, 221 KiB

Open AccessEditorial

Editorial of Special Issue “Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches”

by Vui King Vincent-Chong

Biomedicines 2023, 11(10), 2748; https://doi.org/10.3390/biomedicines11102748 - 11 Oct 2023

Viewed by 671

Abstract

Oral squamous cell carcinoma (OSCC) is a heterogeneous type of malignancy that develops within the oral cavity comprising the lips, tongue, mouth floor, gums, and buccal mucosa, with more than 90% arising from the oral lining epithelium [...] Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

Research

Jump to: Editorial, Review

15 pages, 1275 KiB

Open AccessArticle

The Prognosis Performance of a Neutrophil- and Lymphocyte-Associated Gene Mutation Score in a Head and Neck Cancer Cohort

by Tsung-Jang Yeh, Hui-Ching Wang, Shih-Feng Cho, Chun-Chieh Wu, Tzu-Yu Hsieh, Chien-Tzu Huang, Min-Hong Wang, Tzer-Ming Chuang, Yuh-Ching Gau, Jeng-Shiun Du, Yi-Chang Liu, Hui-Hua Hsiao, Mei-Ren Pan, Li-Tzong Chen and Sin-Hua Moi

Biomedicines 2023, 11(12), 3113; https://doi.org/10.3390/biomedicines11123113 - 22 Nov 2023

Viewed by 818

Abstract

The treatment of head and neck squamous cell carcinomas (HNSCCs) is multimodal, and chemoradiotherapy (CRT) is a critical component. However, the availability of predictive or prognostic markers in patients with HNSCC is limited. Inflammation is a well-documented factor in cancer, and several parameters have been studied, with the neutrophil-to-lymphocyte ratio (NLR) being the most promising. The NLR is the most extensively researched clinical biomarker in various solid tumors, including HNSCC. In our study, we collected clinical and next-generation sequencing (NGS) data with targeted sequencing information from 107 patients with HNSCC who underwent CRT. The difference in the NLR between the good response group and the poor response group was significant, with more patients having a high NLR in the poor response group. We also examined the genetic alterations linked to the NLR and found a total of 41 associated genes across eight common pathways searched from the KEGG database. The overall mutation rate was low, and there was no significant mutation difference between the low- and high-NLR groups. Using a multivariate binomial generalized linear model, we identified three candidate genes (MAP2K2, MAP2K4, and ABL1) that showed significant results and were used to create a gene mutation score (GMS). Using the NLR-GMS category, we noticed that the high-NLR-GMS group had significantly shorter relapse-free survival compared to the intermediate- or low-NLR-GMS groups. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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14 pages, 1290 KiB

Open AccessArticle

Prognostic Significance of β-Catenin in Relation to the Tumor Immune Microenvironment in Oral Cancer

by Paloma Lequerica-Fernández, Tania Rodríguez-Santamarta, Eduardo García-García, Verónica Blanco-Lorenzo, Héctor E. Torres-Rivas, Juan P. Rodrigo, Faustino J. Suárez-Sánchez, Juana M. García-Pedrero and Juan Carlos De Vicente

Biomedicines 2023, 11(10), 2675; https://doi.org/10.3390/biomedicines11102675 - 29 Sep 2023

Cited by 1 | Viewed by 728

Abstract

The aim of this study was to investigate the prognostic relevance of β-catenin expression in oral squamous cell carcinoma (OSCC) and to explore relationships with the tumor immune microenvironment. Expression of β-catenin and PD-L1, as well as lymphocyte and macrophage densities, were evaluated by immunohistochemistry in 125 OSCC patient specimens. Membranous β-catenin expression was detected in 102 (81.6%) and nuclear β-catenin in 2 (1.6%) tumors. There was an association between β-catenin expression, tumoral, and stromal CD8⁺ T-cell infiltration (TIL) and also the type of tumor immune microenvironment (TIME). Tumors harboring nuclear β-catenin were associated with a type II TIME (i.e., immune ignorance defined by a negative PD-L1 expression and low CD8⁺ TIL density), whereas tumors with membranous β-catenin expression were predominantly type IV (i.e., immune tolerance defined by negative PD-L1 and high CD8⁺ TIL density). Combined, but not individual, high stromal CD8⁺ TILs and membranous β-catenin expression was independently associated with better disease-specific survival (HR = 0.48, p = 0.019). Taken together, a combination of high stromal CD8⁺ T-cell infiltration and membranous β-catenin in the tumor emerges as an independent predictor of better survival in OSCC patients. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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16 pages, 5866 KiB

Open AccessArticle

Mometasone Furoate Inhibits the Progression of Head and Neck Squamous Cell Carcinoma via Regulating Protein Tyrosine Phosphatase Non-Receptor Type 11

by Lin Qiu, Qian Gao, Anqi Tao, Jiuhui Jiang and Cuiying Li

Biomedicines 2023, 11(10), 2597; https://doi.org/10.3390/biomedicines11102597 - 22 Sep 2023

Cited by 1 | Viewed by 911

Abstract

Mometasone furoate (MF) is a kind of glucocorticoid with extensive pharmacological actions, including inhibiting tumor progression; however, the role of MF in head and neck squamous cell carcinoma (HNSCC) is still unclear. This study aimed to evaluate the inhibitory effect of MF against HNSCC and investigate its underlying mechanisms. Cell viability, colony formation, cell cycle and cell apoptosis were analyzed to explore the effect of MF on HNSCC cells. A xenograft study model was used to investigate the effect of MF on HNSCC in vivo. The core targets of MF for HNSCC were identified using network pharmacology analysis, TCGA database analysis and real-time PCR. Molecular docking was performed to determine the binding energy. Protein tyrosine phosphatase non-receptor type 11 (PTPN11)-overexpressing cells were constructed, and then, the cell viability and the expression levels of proliferation- and apoptosis-related proteins were detected after treatment with MF to explore the role of PTPN11 in the inhibitory effect of MF against HNSCC. After cells were treated with MF, cell viability and the number of colonies were decreased, the cell cycle was arrested and cell apoptosis was increased. The xenograft study results showed that MF could inhibit cell proliferation via promoting cell apoptosis in vivo. PTPN11 was shown to be the core target of MF against HNSCC via network pharmacology analysis, TCGA database analysis and real-time PCR. The molecular docking results revealed that PTPN11 exhibited the strongest ability to bind to MF. Finally, MF could attenuate the effects of increased cell viability and decreased cell apoptosis caused by PTPN11 overexpression, suggesting that MF can inhibit the progression of HNSCC by regulating PTPN11. MF targeted PTPN11, promoting cell cycle arrest and cell apoptosis, and consequently exerting effective anti-tumor activity. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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15 pages, 9332 KiB

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Development of a Novel Anti-CD44 Variant 7/8 Monoclonal Antibody, C₄₄Mab-34, for Multiple Applications against Oral Carcinomas

by Hiroyuki Suzuki, Kazuki Ozawa, Tomohiro Tanaka, Mika K. Kaneko and Yukinari Kato

Biomedicines 2023, 11(4), 1099; https://doi.org/10.3390/biomedicines11041099 - 05 Apr 2023

Cited by 6 | Viewed by 1608

Abstract

Cluster of differentiation 44 (CD44) has been investigated as a cancer stem cell (CSC) marker as it plays critical roles in tumor malignant progression. The splicing variants are overexpressed in many carcinomas, especially squamous cell carcinomas, and play critical roles in the promotion of tumor metastasis, the acquisition of CSC properties, and resistance to treatments. Therefore, each CD44 variant (CD44v) function and distribution in carcinomas should be clarified for the establishment of novel tumor diagnosis and therapy. In this study, we immunized mouse with a CD44 variant (CD44v3–10) ectodomain and established various anti-CD44 monoclonal antibodies (mAbs). One of the established clones (C₄₄Mab-34; IgG₁, kappa) recognized a peptide that covers both variant 7- and variant 8-encoded regions, indicating that C₄₄Mab-34 is a specific mAb for CD44v7/8. Moreover, C₄₄Mab-34 reacted with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO) cells or the oral squamous cell carcinoma (OSCC) cell line (HSC-3) by flow cytometry. The apparent K_D of C₄₄Mab-34 for CHO/CD44v3–10 and HSC-3 was 1.4 × 10⁻⁹ and 3.2 × 10⁻⁹ M, respectively. C₄₄Mab-34 could detect CD44v3–10 in Western blotting and stained the formalin-fixed paraffin-embedded OSCC in immunohistochemistry. These results indicate that C₄₄Mab-34 is useful for detecting CD44v7/8 in various applications and is expected to be useful in the application of OSCC diagnosis and therapy. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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14 pages, 2625 KiB

Open AccessArticle

IFIT2 Depletion Promotes Cancer Stem Cell-like Phenotypes in Oral Cancer

by Kuo-Chu Lai, Prabha Regmi, Chung-Ji Liu, Jeng-Fan Lo and Te-Chang Lee

Biomedicines 2023, 11(3), 896; https://doi.org/10.3390/biomedicines11030896 - 14 Mar 2023

Cited by 2 | Viewed by 1519

Abstract

(1) Background: Cancer stem cells (CSCs) are a small cell population associated with chemoresistance, metastasis and increased mortality rate in oral cancer. Interferon-induced proteins with tetratricopeptide repeats 2 (IFIT2) depletion results in epithelial to mesenchymal transition, invasion, metastasis, and chemoresistance in oral cancer. To date, no study has demonstrated the effect of IFIT2 depletion on the CSC-like phenotype in oral cancer cells. (2) Methods: Q-PCR, sphere formation, Hoechst 33,342 dye exclusion, immunofluorescence staining, and flow cytometry assays were performed to evaluate the expression of the CSC markers in IFIT2-depleted cells. A tumorigenicity assay was adopted to assess the tumor formation ability. Immunohistochemical staining was used to examine the protein levels of IFIT2 and CD24 in oral cancer patients. (3) Results: The cultured IFIT2 knockdown cells exhibited an overexpression of ABCG2 and CD44 and a downregulation of CD24 and gave rise to CSC-like phenotypes. Clinically, there was a positive correlation between IFIT2 and CD24 in the patients. IFIT2^high/CD24^high/CD44^low expression profiles predicted a better prognosis in HNC, including oral cancer. The TNF-α blockade abolished the IFIT2 depletion-induced sphere formation, indicating that TNF-α may be involved in the CSC-like phenotypes in oral cancer. (4) Conclusions: The present study demonstrates that IFIT2 depletion promotes CSC-like phenotypes in oral cancer. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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12 pages, 3407 KiB

Open AccessArticle

Deep-Learning-Based Automated Identification and Visualization of Oral Cancer in Optical Coherence Tomography Images

by Zihan Yang, Hongming Pan, Jianwei Shang, Jun Zhang and Yanmei Liang

Biomedicines 2023, 11(3), 802; https://doi.org/10.3390/biomedicines11030802 - 06 Mar 2023

Cited by 8 | Viewed by 2419

Abstract

Early detection and diagnosis of oral cancer are critical for a better prognosis, but accurate and automatic identification is difficult using the available technologies. Optical coherence tomography (OCT) can be used as diagnostic aid due to the advantages of high resolution and non-invasion. We aim to evaluate deep-learning-based algorithms for OCT images to assist clinicians in oral cancer screening and diagnosis. An OCT data set was first established, including normal mucosa, precancerous lesion, and oral squamous cell carcinoma. Then, three kinds of convolutional neural networks (CNNs) were trained and evaluated by using four metrics (accuracy, precision, sensitivity, and specificity). Moreover, the CNN-based methods were compared against machine learning approaches through the same dataset. The results show the performance of CNNs, with a classification accuracy of up to 96.76%, is better than the machine-learning-based method with an accuracy of 92.52%. Moreover, visualization of lesions in OCT images was performed and the rationality and interpretability of the model for distinguishing different oral tissues were evaluated. It is proved that the automatic identification algorithm of OCT images based on deep learning has the potential to provide decision support for the effective screening and diagnosis of oral cancer. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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12 pages, 919 KiB

Open AccessArticle

Psychosocial Adjustment Changes and Related Factors in Postoperative Oral Cancer Patients: A Longitudinal Study

by Yi-Wei Chen, Ting-Ru Lin, Pei-Ling Kuo, Shu-Chiung Lee, Kuo-Feng Wu, Tuyen Van Duong and Tsae-Jyy Wang

Biomedicines 2022, 10(12), 3231; https://doi.org/10.3390/biomedicines10123231 - 12 Dec 2022

Cited by 3 | Viewed by 1636

Abstract

Disease and treatment-related symptoms and dysfunctions can interfere with the psychosocial adjustment of patients with oral cancer. Identifying factors influencing psychosocial maladjustment is important because at-risk individuals can be targeted for early intervention. This prospective longitudinal study investigated psychosocial adjustment changes and associated factors in postoperative oral cancer patients. Data on psychosocial adjustment, facial disfigurement, symptoms, and social support were collected before surgery (T1) at one month (T2), three months (T3), and five months after discharge (T4). Fifty subjects completed the study, and their data were included in the analysis. Psychosocial maladjustment was reported in 50%, 59.2%, 66%, and 62% of subjects at T1, T2, T3, and T4, respectively. The subjects’ psychosocial adjustment deteriorated after surgery. Results from generalized estimating equations indicated that financial status, cancer stage, pain, speech problems, social eating problems, and less sexuality were significant predictors of changes in psychosocial adjustment. Patients with insufficient income, stage III/IV cancer, severe pain, speech problems, social eating problems, and less sexuality were at higher risk for postoperative psychosocial maladjustment. Continued psychosocial assessment and appropriate supportive measures are needed to strengthen the psychosocial adjustment of these high-risk groups. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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8 pages, 1308 KiB

Open AccessCommunication

Lymph Node Ratio in Head and Neck Cancer with Submental Flap Reconstruction

by Hidenori Suzuki, Shintaro Beppu, Daisuke Nishikawa, Hoshino Terada, Michi Sawabe and Nobuhiro Hanai

Biomedicines 2022, 10(11), 2923; https://doi.org/10.3390/biomedicines10112923 - 14 Nov 2022

Cited by 1 | Viewed by 3314

Abstract

This study aimed to investigate the relationship between the lymph node ratio (LNR) and survival results of patients with head and neck squamous cell carcinoma (HNSCC) reconstructed by a submental artery flap (SMAF) to limit tumor size. This study retrospectively recruited 49 patients with HNSCC who underwent both primary resection and neck dissection with SMAF reconstruction. The LNR was the ratio of the number of metastatic lymph nodes to the sum number of examined lymph nodes. A LNR of 0.04 was the best cut-off value for HNSCC-specific death on receiver operating curve analysis. Patients with LNRs > 0.04 were univariately related to cancer-specific, disease-free, distant metastasis-free, and locoregional recurrence-free survival than those with LNRs ≤ 0.04 by log-rank test. In a Cox’s proportional hazards model with hazard ratio (HR) and 95% confidence interval (CI) adjusting for pathological stage, extranodal extension and or surgical margins, the LNR (>0.04/≤0.04) predicted multivariate shorter cancer-specific (HR = 9.24, 95% CI = 1.49–176), disease-free (HR = 3.44, 95% CI = 1.23–10.3), and distant metastasis-free (HR = 9.76, 95% CI = 1.57–187) survival. In conclusion, LNR for patients of HNSCC with SMAF reconstruction for limited tumor size was a prognostic factor for survival outcomes. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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11 pages, 2194 KiB

Open AccessArticle

T-Cell Infiltration and Immune Checkpoint Expression Increase in Oral Cavity Premalignant and Malignant Disorders

by Subin Surendran, Usama Aboelkheir, Andrew A. Tu, William J. Magner, S. Lynn Sigurdson, Mihai Merzianu, Wesley L. Hicks, Jr., Amritha Suresh, Keith L. Kirkwood and Moni A. Kuriakose

Biomedicines 2022, 10(8), 1840; https://doi.org/10.3390/biomedicines10081840 - 30 Jul 2022

Cited by 4 | Viewed by 1745

Abstract

The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly understood. We identified T regulatory cells (Treg), CD8⁺ effector T cells (Teff) and immune checkpoint molecules across oral dysplastic stages of oral potentially malignant disorders (OPMD). OPMD and oral squamous cell carcinoma (OSCC) tissue sections (N = 270) were analyzed by immunohistochemistry for Treg (CD4, CD25 and FoxP3), Teff (CD8) and immune checkpoint molecules (PD-1 and PD-L1). The Treg marker staining intensity correlated significantly (p < 0.01) with presence of higher dysplasia grade and invasive cancer. These data suggest that Treg infiltration is relatively early in dysplasia and may be associated with disease progression. The presence of CD8⁺ effector T cells and the immune checkpoint markers PD-1 and PD-L1 were also associated with oral cancer progression (p < 0.01). These observations indicate the induction of an adaptive immune response with similar Treg and Teff recruitment timing and, potentially, the early induction of exhaustion. FoxP3 and PD-L1 levels were closely correlated with CD8 levels (p < 0.01). These data indicate the presence of reinforcing mechanisms contributing to the immune suppressive niche in high-risk OPMD and in OSCC. The presence of an adaptive immune response and T-cell exhaustion suggest that an effective immune response may be reactivated with targeted interventions coupled with immune checkpoint inhibition. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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15 pages, 1530 KiB

Open AccessArticle

Prognostic Role of Systemic Inflammatory Markers in Patients Undergoing Surgical Resection for Oral Squamous Cell Carcinoma

by Uiju Cho, Yeoun-Eun Sung, Min-Sik Kim and Youn-Soo Lee

Biomedicines 2022, 10(6), 1268; https://doi.org/10.3390/biomedicines10061268 - 29 May 2022

Cited by 8 | Viewed by 1843

Abstract

Background: A high platelet–lymphocyte ratio (PLR) is a marker of systemic inflammation and, together with the neutrophil–lymphocyte ratio (NLR), is associated with poor outcomes in several cancers. We investigated the prognostic value of PLR and other systemic inflammatory markers, such as NLR, systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), in oral squamous cell carcinoma (OSCC) patients undergoing surgical resection. Methods: We derived PLR, NLR, SII, and SIRI from a retrospective chart review of 269 consecutive OSCC patients. The complete blood count examined in the immediate preoperative period was used to compute PLR, NLR, SII, and SIRI. We analyzed the relationship between these systemic inflammatory markers and the clinicopathologic characteristics, disease-specific survival (DSS), and progression-free survival (PFS) of patients. Results: In the univariate analysis, high PLR and SII were significantly associated with worse DSS and PFS (all p < 0.05). In the multivariate analysis, PLR (HR 2.36, 95% CI 1.28–4.36 for DSS; HR 1.80, 95% CI 1.06–3.06 for PFS) was an independent predictor of survival outcomes. When PLR was analyzed as a continuous variable, the relationship between the outcome and preoperative PLR was not monotonically linear. In the subgroup analysis, PLR was more strongly associated with DSS and PFS in patients who were male, had stage III/IV OSCC, or had lymph node metastasis. Conclusion: Our data suggest that in OSCC patients, the pretreatment PLR is an independent predictor of DSS and PFS. The PLR is a readily available biomarker that will improve prognostication and risk stratification in OSCC. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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Review

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27 pages, 2045 KiB

Open AccessReview

A Comprehensive Review of Natural Products as Therapeutic or Chemopreventive Agents against Head and Neck Squamous Cell Carcinoma Cells Using Preclinical Models

by Yoon Xuan Liew, Lee Peng Karen-Ng and Vui King Vincent-Chong

Biomedicines 2023, 11(9), 2359; https://doi.org/10.3390/biomedicines11092359 - 23 Aug 2023

Cited by 1 | Viewed by 1075

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that arises from the epithelium lining of the oral cavity, hypopharynx, oropharynx, and larynx. Despite the advancement of current treatments, including surgery, chemotherapy, and radiotherapy, the overall survival rate of patients afflicted with HNSCC remains poor. The reasons for these poor outcomes are due to late diagnoses and patient-acquired resistance to treatment. Natural products have been extensively explored as a safer and more acceptable alternative therapy to the current treatments, with numerous studies displaying their potential against HNSCC. This review highlights preclinical studies in the past 5 years involving natural products against HNSCC and explores the signaling pathways altered by these products. This review also addresses challenges and future directions of natural products as chemotherapeutic and chemoprevention agents against HNSCC. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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18 pages, 1449 KiB

Open AccessReview

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

by 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 and Sin-Hua Moi

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

Cited by 2 | Viewed by 2480

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. Full article

(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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