Head and Neck Pathology

, Volume 4, Issue 1, pp 62–69

Integration of Biomarkers Including Molecular Targeted Therapies in Head and Neck Cancer

PROCEEDINGS OF THE 2010 NORTH AMERICAN SOCIETY OF HEAD AND NECK PATHOLOGY COMPANION MEETING (WASHINGTON, DC)
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Abstract

Head and neck tumors comprise a wide spectrum of heterogeneous neoplasms for which biomarkers are needed to aid in earlier diagnosis, risk assessment and therapy response. The search for biomarkers includes evaluation of tumor tissues and surrogate materials by molecular, genomic and phenotypic means. Ideal biomarkers should be accurate and easy to perform, highly specific, objective, quantitative, and cost effective. Because of the heterogeneity of head and neck tumors, the integration of multiple selected markers in association with the histopathologic features is advocated for risk assessment. For targeted therapy, however, a single key molecule must be identified. Key molecules and pathways for targeted therapy include growth factor receptors, MAPk/ERk pathway, angiogenesis, and epithelial to mesenchymal transition. Over-expression and mutations of genes in these pathways including EGFR, VEGF, HER2, BRAF and RET, contribute to tumorigenesis in head and neck cancers from squamous carcinomas, to salivary adenocarcinomas and thyroid carcinomas, both follicular and c-cell derived. Monoclonal antibodies to the EGFR receptor and oral tyrosine kinase inhibitors are currently being studied in multiple phase II and III clinical trials to determine their efficacy in head and neck cancers and correlative studies for biomarkers are on-going.

Keywords

Biomarkers Squamous carcinoma EGFR Molecular targets Head and neck cancer 

References

  1. 1.
    Mao L, Lee JS, Fan YH, Ro JY, Batsakis JG, Lippman S, et al. Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment. Nat Med. 1996;2:682–5.CrossRefPubMedGoogle Scholar
  2. 2.
    Poeta ML, Manola J, Goldwasser MA, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med. 2007;357:2552–61.CrossRefPubMedGoogle Scholar
  3. 3.
    Cho WC. Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer. 2007;6:1.CrossRefPubMedGoogle Scholar
  4. 4.
    Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, et al. Molecular classification identifies a subset of human papillomavirus–associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 2006;24:736–47.CrossRefPubMedGoogle Scholar
  6. 6.
    Chai RL, Grandis JR. Advances in molecular diagnostics and therapeutics in head and neck cancer. Curr Treat Options Oncol. 2006;7:3–11.CrossRefPubMedGoogle Scholar
  7. 7.
    Ang KK, Berkey BA, Tu X, Zhang HZ, Katz R, Hammond EH, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62:7350–6.PubMedGoogle Scholar
  8. 8.
    Kim S, Grandis JR, Rinaldo A, Takes RP, Ferlito A. Emerging perspectives in epidermal growth factor receptor targeting in head and neck cancer. Head Neck. 2008;30:667–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Sok JC, Coppelli FM, Thomas SM, et al. Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin Cancer Res. 2006;12:5064–73.CrossRefPubMedGoogle Scholar
  10. 10.
    Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–78.CrossRefPubMedGoogle Scholar
  11. 11.
    Howell GM, Grandis JR. Molecular mediators of metastasis in head and neck squamous cell carcinoma. Head Neck. 2005;27:710–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Mandal M, Myers JN, Lippman SM, Johnson FM, Williams MD, Rayala S, et al. Epithelial to mesenchymal transition in head and neck squamous carcinoma: association of Src activation with E-cadherin down-regulation, vimentin expression, and aggressive tumor features. Cancer. 2008;112:2088–100.CrossRefPubMedGoogle Scholar
  13. 13.
    Hu S, Arellano M, Boontheung P, Wang J, Zhou H, Jiang J, et al. Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res. 2008;14:6246–52.CrossRefPubMedGoogle Scholar
  14. 14.
    Elledge R. Current concepts in research related to oncogenes implicated in salivary gland tumourigenesis: a review of the literature. Oral Dis. 2009;15:249–54.CrossRefPubMedGoogle Scholar
  15. 15.
    Tirado Y, Williams MD, Hanna EY, Kaye FJ, Batsakis JG, El-Naggar AK. CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin’s tumors: implications for histogenesis and biologic behavior. Genes Chromosomes Cancer. 2007;46:708–15.CrossRefPubMedGoogle Scholar
  16. 16.
    Persson M, Andren Y, Mark J, Horlings HM, Persson F, Stenman G. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci U S A. 2009;106:18740–4.CrossRefPubMedGoogle Scholar
  17. 17.
    Rao PH, Roberts D, Zhao YJ, Bell D, Harris CP, Weber RS, et al. Deletion of 1p32–p36 is the most frequent genetic change and poor prognostic marker in adenoid cystic carcinoma of the salivary glands. Clin Cancer Res. 2008;14:5181–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Nikiforova MN, Nikiforov YE. Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis. Expert Rev Mol Diagn. 2008;8:83–95.CrossRefPubMedGoogle Scholar
  19. 19.
    Morabito A, Piccirillo MC, Falasconi F, De Feo G, Del Giudice A, Bryce J, et al. Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: current status and future directions. Oncologist. 2009;14:378–90.CrossRefPubMedGoogle Scholar
  20. 20.
    Weigum SE, Floriano PN, Christodoulides N, McDevitt JT. Cell-based sensor for analysis of EGFR biomarker expression in oral cancer. Lab Chip. 2007;7:995–1003.CrossRefPubMedGoogle Scholar

Copyright information

© Humana 2010

Authors and Affiliations

  1. 1.Department of PathologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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