Telomeres and telomerase in head and neck squamous cell carcinoma: from pathogenesis to clinical implications

Abstract

Strongly associated with tobacco use, heavy alcohol consumption, and with high-risk human papillomavirus (HPV) infection, head and neck squamous cell carcinoma (HNSCC) is a frequently lethal, heterogeneous disease whose pathogenesis is a multistep and multifactorial process involving genetic and epigenetic events. The majority of HNSCC patients present with locoregional advanced stage disease and are treated with combined modality strategies that can markedly impair quality of life and elicit unpredictable results. A large fraction of those who undergo locoregional treatment and achieve a complete response later develop locoregional recurrences or second field tumors. Biomarkers that are thus able to stratify risk and enable clinicians to tailor treatment plans and to personalize post-therapeutic surveillance strategies are highly desirable. To date, only HPV status is considered a reliable independent predictor of treatment response and survival in patients with HNSCC arising from the oropharyngeal site. Recent studies suggest that telomere attrition, which may be an early event in human carcinogenesis, and telomerase activation, which is detected in up to 90 % of malignancies, could be potential markers of cancer risk and disease outcome. This review examines the current state of knowledge on and discusses the implications linked to telomere dysfunction and telomerase activation in the development and clinical outcome of HNSCC.

The Telomerase and Alternative Lengthening of Telomeres Mechanisms Regulate Laryngeal Cancer Cell Apoptosis via the PI3K/Akt Pathway

“…Recently, the targeting of telomeres gained much attention for its therapeutic anticancer effects [14][15][16]. In this study, we confirmed that silencing the genes related to telomerase and ALT mechanisms is associated with inhibiting tumor growth in vivo, consistent with our previously published results [9].…”

Short telomere length in peripheral blood leukocytes in head and neck cancer: Findings in a Brazilian cohort

“…18,19 Different studies observed that patients with short telomeres have a higher risk of developing HNC. [9][10][11][12]18,20 Short LTL associated with an increased risk of developing oral premalignant lesions (OPL) and oral squamous cell carcinoma (OSCC), suggesting that patients with OPL and short LTL have an increased risk to progress to OSCC. Indeed, patients who have OSCC and short LTL have the worst prognosis.…”

“…However, the association between telomere length (TL) and the risk of developing cancers is still conflicting among studies. [9][10][11][12] The head and neck cancer (HNC) represents the sixth most common cancer worldwide. 5 Non-small cell lung tumors present shorter telomeres compared with telomeres in control tissues.…”

“…These findings support the hypothesis that genomic instability driven by telomere dysfunction is an early event in the HNSCC oncogenetic process. [9][10][11][12] The head and neck cancer (HNC) represents the sixth most common cancer worldwide. In every year, more than 600 000 patients are diagnosed with HNC, resulting in more than 350 000 deaths.…”

Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: Current knowledge and future implications

“…Checkpoint-compromised cells can escape cellular senescence and apoptosis and potentially reactivate telomerase expression to drive telomere maintenance and replicative immortality. 67 There is growing interest in studying the interplay of telomere/ telomerase as a key determinant for genomic stability, with most studies indicating that they are detectable at the premalignant stage of various cancer types. 68 However, there are no studies assessing the telomeres in PPOELs.…”