Dataset Information

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.

SUBMITTER: Boscolo-Rizzo P

PROVIDER: S-EPMC5035656 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Boscolo-Rizzo Paolo P Da Mosto Maria Cristina MC Rampazzo Enrica E Giunco Silvia S Del Mistro Annarosa A Menegaldo Anna A Baboci Lorena L Mantovani Monica M Tirelli Giancarlo G De Rossi Anita A

Cancer metastasis reviews 20160901 3

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 un ...[more]

PMID: 27501725

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Project description:The literature contains numerous references describing heterogeneity for tumor phenotypes including cell proliferation, invasiveness, metastatic potential, and response to therapies. However, data regarding angiogenic heterogeneity are limited. In this study, we investigated the degree of intertumoral angiogenic heterogeneity present in head and neck squamous cell carcinomas (HNSCC). In addition, we investigated the biological relevance that this heterogeneity may have in the context of cytokine directed antiangiogenic therapy. Keratinocytes were harvested from HNSCC specimens using laser capture microdissection (LCM). Gene expression profiling of the RNA extracted from these specimens demonstrated variability in the expression of angiogenesis-related genes. Hierarchical clustering and principal component analyses (PCA) demonstrated the presence of unique patient clusters, suggesting that there may be two potentially distinct pathways by which HNSCC induce angiogenesis. Immunohistochemistry for VEGF, IL-8/CXCL8, HGF, and FGF-2, cytokines that play functional roles in HNSCC angiogenesis was performed on the original patient samples as well as a larger panel of normal, dysplastic and HNSCC specimens to validate the heterogeneous expression observed in the gene expression profiling studies. Finally, the therapeutic response of HNSCC tumor xenografts to anti-VEGF therapy was found to be dependent on the amount of VEGF produced by the tumor cells. These findings support the hypothesis of intertumoral angiogenic heterogeneity. They imply that there are differences with regard to the specific molecular mechanisms by which individual tumors within the same histological type induce angiogenesis. Moreover, they demonstrate the need for a more in-depth understanding of the variability of the angiogenic phenotype within a given type of neoplasm when designing cytokine targeted antiangiogenic therapies. Finally, they suggest that studies in conjunction with the ongoing clinical trials that explore the correlation between target expression and clinical outcome are warranted.

Dataset Information

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

Publications

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

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