The molecular pathogenesis of head and neck squamous cell carcinoma

Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts 02114, USA.
The Journal of clinical investigation (Impact Factor: 13.77). 06/2012; 122(6):1951-7. DOI: 10.1172/JCI59889
Source: PubMed

ABSTRACT Squamous cell carcinoma of the head and neck (HNSCC) is a relatively common human cancer characterized by high morbidity, high mortality, and few therapeutic options outside of surgery, standard cytotoxic chemotherapy, and radiation. Although the most important risk factors are tobacco use and alcohol consumption, the disease is also linked to infection with high-risk types of human papilloma viruses (HPVs). Recent genetic analyses have yielded new insights into the molecular pathogenesis of this disease. Overall, while somatic activating mutations within classical oncogenes including PIK3CA and RAS occur in HNSCC, they are relatively uncommon. Instead genetic data point to a contribution of multiple tumor suppressor pathways, including p53, Rb/INK4/ARF, and Notch, in tumor initiation, progression, and maintenance. The increasingly refined knowledge of HNSCC genetics, combined with ever-more-sophisticated animal models and newer drug targeting strategies, should promote novel therapeutic approaches and improved disease outcomes.

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    • "Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer globally, affects 600,000 new patients each year and is associated with high morbidity [1]. The most common sites for HNSCC are the pharynx/larynx, tongue and mouth [2]. "
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) represent 95% of head and neck cancer with an incidence of over half a million people globally. The prognosis for patients with recurrent or metastatic HNSCC is generally poor with low 5-year survival rates despite treatment advances over the past few decades. Consequently, it is essential to search for new biomarkers and effective therapy options to optimize HNSCC treatment. Epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of tumours. EGFR has become one of most common targets for new therapies being investigated in HNSCC. In this way, multiple therapies targeting EGFR in HNSCC have been tested but response rates are still low especially in the recurrent or metastatic setting. This has been attributed to mechanisms of resistance to EGFR-targeted therapies. Afatinib, an oral small molecule ErbB Family Blocker that irreversibly binds to ErbB1 (EGFR), ErbB2 (HER2) and ErbB4 (HER4), is being investigated in HNSCC treatment with encouraging phase II results and several ongoing phase III trials. Results of these trials will help to understand the place of afatinib in the HNSCC treatment armamentarium. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Oral Oncology 03/2015; 122(5). DOI:10.1016/j.oraloncology.2015.02.092 · 3.03 Impact Factor
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    • "However, the details of the mechanism of cancer transformation and tumor progression still remain uncertain [1] [3]. The evaluation of alternations between the expression of biological markers expressed by tumor cells, as well as in tumoral stroma cells, might lead to investigate novel therapeutic approaches in identification of the novel molecular targets for therapy [1]. Laryngeal cancers still cause the diagnostic and therapeutic problems, mainly as consequence of diagnostic delay related to the advanced stage of the disease in patients at the moment of diagnosis. "
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    ABSTRACT: Purpose Laryngeal squamous cell carcinoma (LSCC) is an interesting diagnostic and therapeutic issue. The diagnostic delay is mainly a consequence of the lack of evident symptoms in the early stage of the disease. The purpose of current studies was the evaluation of the expression of p27kip1 in primary and metastatic LSCC in correlation with patients’ clinicopathological data. Material/methods The indirect immunohistochemical studies were performed on the series of 60 sections (primary tumor: 20 cases of N(0) and 20 cases of N(+), and nodal meta: 20 cases), using primary antibody against p27kip1 [clone 1B4]. The expression of analyzed protein was performed using automated morphometric methods. Results The p27kip1 nuclear expression was found in 100% (40/40) cases of primary tumor, and in 85% (17/20) cases of SCC meta at lymph nodes. In primary LSCC N(0) the expression of p27kip1 was significantly higher compared to N(+) cases (p = 0.036672). However, the p27kip1 expression in SCC metastases was higher compared to the primary SCC. Moreover, the analyses based on the classification trees revealed the cutoff p27kip1 expression in primary LSCC (IRS ≤ 76) which was characteristic for N(+) patients. Consequently, our analysis revealed that high expression of p27kip1 (IRS > 76) was characteristic for N(0) patients. Conclusions Our results suggest that p27kip1 might be useful prognostic factor of metastatic potential in laryngeal squamous cell carcinoma.
    Advances in Medical Sciences 09/2014; DOI:10.1016/j.advms.2014.03.005 · 0.96 Impact Factor
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    • "In Southeast Asia, oral cancer shows the highest incidence and prevalence due to influence of tobacco and betel quid chewing habits [11]. High-risk human papilloma viruses (HR-HPVs) and Epstein-Barr virus (EBV) have also been identified as increasingly important risk factors [12] [13] [14] [15] [16]. Within the spectrum of oral malignancies, almost 90 percent are squamous cell carcinomas (SCC) [17]. "
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    ABSTRACT: Abnormal chromosome number, or aneuploidy, is a common feature of human solid tumors, including oral cancer. Deregulated spindle assembly checkpoint (SAC) is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic stability. Significantly, the activity of this checkpoint is compromised in many cancers. While mutations are rather rare, many tumors show altered expression levels of SAC components. Genomic alterations such as aneuploidy indicate a high risk of oral cancer and cancer-related mortality, and the molecular basis of these alterations is largely unknown. Yet, our knowledge on the status of SAC components in oral cancer remains sparse. In this review, we address the state of our knowledge regarding the SAC defects and the underlying molecular mechanisms in oral cancer, and discuss their therapeutic relevance, focusing our analysis on the core components of SAC and its target Cdc20.
    BioMed Research International 06/2014; 2014:145289. DOI:10.1155/2014/145289 · 2.71 Impact Factor
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