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      Clinical update on cancer: molecular oncology of head and neck cancer

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          Abstract

          Head and neck cancers encompass a heterogeneous group of tumours that, in general, are biologically aggressive in nature. These cancers remain difficult to treat and treatment can cause severe, long-term side effects. For patients who are not cured by surgery and/or (chemo)radiotherapy, there are few effective treatment options. Targeted therapies and predictive biomarkers are urgently needed in order to improve the management and minimise the treatment toxicity, and to allow selection of patients who are likely to benefit from both nonselective and targeted therapies. This clinical update aims to provide an insight into the current understanding of the molecular pathogenesis of the disease, and explores the novel therapies under development and in clinical trials.

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          TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis

          Karim Bensaad, Atsushi Tsuruta, Mary A. Selak … (2006)
          The p53 tumor-suppressor protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability. We have identified a p53-inducible gene named TIGAR (TP53-induced glycolysis and apoptosis regulator). TIGAR expression lowered fructose-2,6-bisphosphate levels in cells, resulting in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death. Expression of TIGAR may therefore modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired. The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage.
          Article 0 comments Cited 642 times – based on 0 reviews     Review now
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            Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.

            N. Agrawal, M Frederick, C. R. Pickering … (2011)
            Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.
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              Head and neck cancer.

              Athanassios Argiris, Michalis V. Karamouzis, David Raben … (2008)
              Most head and neck cancers are squamous cell carcinomas that develop in the upper aerodigestive epithelium after exposure to carcinogens such as tobacco and alcohol. Human papillomavirus has also been strongly implicated as a causative agent in a subset of these cancers. The complex anatomy and vital physiological role of the tumour-involved structures dictate that the goals of treatment are not only to improve survival outcomes but also to preserve organ function. Major improvements have been accomplished in surgical techniques and radiotherapy delivery. Moreover, systemic therapy including chemotherapy and molecularly targeted agents--namely, the epidermal growth factor receptor inhibitors--has been successfully integrated into potentially curative treatment of locally advanced squamous-cell carcinoma of the head and neck. In deciding which treatment strategy would be suitable for an individual patient, important considerations include expected functional outcomes, ability to tolerate treatment, and comorbid illnesses. The collaboration of many specialties is the key for optimum assessment and decision making. We review the epidemiology, molecular pathogenesis, diagnosis and staging, and the latest multimodal management of squamous cell carcinoma of the head and neck.
              Article 0 comments Cited 531 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cell Death Dis
                Journal ID (iso-abbrev): Cell Death Dis
                Title: Cell Death & Disease
                Publisher: Nature Publishing Group
                ISSN (Electronic): 2041-4889
                Publication date (Print): January 2014
                Publication date (Electronic): 23 January 2014
                Publication date PMC-release: 1 January 2014
                Volume: 5
                Issue: 1
                Page: e1018
                Affiliations
                [1 ]Department of Molecular Oncology, King's College London, Guy's Hospital, Hodgkin Building , London SE1 1NU, UK
                [2 ]Medical Research Council, Toxicology Unit, Leicester University , Leicester LE1 9HN, UK
                [3 ]Clinical Oncology Department, Lambeth Wing, St Thomas' Hospital, Westminster Bridge Road , London SE1 7EH, UK
                Author notes
                [* ]Department of Molecular Oncology, Head and Neck Oncology Group, Dental Institute, King's College London , Hodgkin Building, London SE1 1UL, UK. Tel: +44 (0)20 7848 6109; Fax: +44 (0)20 7848 6210; E-mail: Mahvash.tavassoli@ 123456kcl.ac.uk
                Article
                Publisher Item ID: cddis2013548
                DOI: 10.1038/cddis.2013.548
                PMC ID: 4040714
                PubMed ID: 24457962
                SO-VID: be0aad43-35ee-4fac-9580-f76159da8c73
                Copyright © Copyright © 2014 Macmillan Publishers Limited
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                Date received : 04 November 2013
                Date revision received : 04 December 2013
                Date accepted : 05 December 2013
                Categories
                Subject: Review

                ScienceOpen disciplines: Cell biology
                Keywords: head and neck squamous cell carcinoma,targeted therapy,hpv,metabolism,hypoxia,biomarkers
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: head and neck squamous cell carcinoma, targeted therapy, hpv, metabolism, hypoxia, biomarkers

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