Advertisement

Overview: The Pathobiology of Head and Neck Cancer

  • Barbara Burtness
  • Erica A. Golemis
Chapter
Part of the Current Cancer Research book series (CUCR)

Abstract

Squamous cell cancers arising in the head and neck, from the nasopharynx to the subglottic larynx, are frequently devastating cancers that afflict patients around the world. Early stage cancers are readily cured with surgery or radiation. In contrast, locally advanced cancers require morbid multimodality therapy and nonetheless have high recurrence rates, while metastatic disease has not been curable with cytotoxic chemotherapy. The emergence of more treatment-responsive human papillomavirus (HPV)-driven cancers and the advent of immune checkpoint blockade mean that the outlook for patients with head and neck cancer has improved dramatically since the first edition of this book was published in 2014. Our understanding of the biology of this cancer has deepened considerably in the past 4 years, yet undruggable targets due to the predominance of tumor suppressor gene mutation and other noncatalytic abnormalities continue to present barriers to molecular and personalized therapy and to cure in HPV-negative disease.

References

  1. 1.
    Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23:8646–54.CrossRefPubMedGoogle Scholar
  2. 2.
    Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.CrossRefPubMedGoogle Scholar
  3. 3.
    Seiwert TY, Jagadeeswaran R, Faoro L, Janamanchi V, Nallasura V, El Dinali M, Yala S, Kanteti R, Cohen EE, Lingen MW, Martin L, Krishnaswamy S, Klein-Szanto A, Christensen JG, Vokes EE, Salgia R. The MET receptor tyrosine kinase is a potential novel therapeutic target for head and neck squamous cell carcinoma. Cancer Res. 2009;69:3021–31.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    White RA, Malkoski SP, Wang XJ. TGFbeta signaling in head and neck squamous cell carcinoma. Oncogene. 2010;29:5437–46.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bauman JE, Arias-Pulido H, Lee SJ, Fekrazad MH, Ozawa H, Fertig E, Howard J, Bishop J, Wang H, Olson GT, Spafford MJ, Jones DV, Chung CH. A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma. Oral Oncol. 2013;49:461–7.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Leeman RJ, Lui VW, Grandis JR. STAT3 as a therapeutic target in head and neck cancer. Expert Opin Biol Ther. 2006;6:231–41.CrossRefPubMedGoogle Scholar
  7. 7.
    Rothenberg SM, Ellisen LW. The molecular pathogenesis of head and neck squamous cell carcinoma. J Clin Invest. 2012;122:1951–7.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Trevino L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333:1154–7.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Skinner HD, Sandulache VC, Ow TJ, Meyn RE, Yordy JS, Beadle BM, Fitzgerald AL, Giri U, Ang KK, Myers JN. TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res. 2012;18:290–300.CrossRefPubMedGoogle Scholar
  10. 10.
    Faden DL, Thomas S, Cantalupo PG, Agrawal N, Myers J, DeRisi J. Multi-modality analysis supports APOBEC as a major source of mutations in head and neck squamous cell carcinoma. Oral Oncol. 2017;74:8–14.CrossRefPubMedGoogle Scholar
  11. 11.
    Henderson S, Chakravarthy A, Su X, Boshoff C, Fenton TR. APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to human papillomavirus-driven tumor development. Cell Rep. 2014;7:1833–41.CrossRefPubMedGoogle Scholar
  12. 12.
    Ling DC, Bakkenist CJ, Ferris RL, Clump DA. Role of immunotherapy in head and neck cancer. Semin Radiat Oncol. 2018;28:12–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Rischin D, Fisher R, Peters L, Corry J, Hicks R. Hypoxia in head and neck cancer: studies with hypoxic positron emission tomography imaging and hypoxic cytotoxins. Int J Radiat Oncol Biol Phys. 2007;69:S61–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Vassilakopoulou M, Psyrri A, Argiris A. Targeting angiogenesis in head and neck cancer. Oral Oncol. 2015;51:409–15.CrossRefPubMedGoogle Scholar
  15. 15.
    Skinner HD, Giri U, Yang L, Woo SH, Story MD, Pickering CR, Byers LA, Williams MD, El-Naggar A, Wang J, Diao L, Shen L, Fan YH, Molkentine DP, Beadle BM, Meyn RE, Myers JN, Heymach JV. Proteomic profiling identifies PTK2/FAK as a driver of radioresistance in HPV-negative head and neck cancer. Clin Cancer Res. 2016;22:4643–50.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Rhee CS, Sen M, Lu D, Wu C, Leoni L, Rubin J, Corr M, Carson DA. Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas. Oncogene. 2002;21:6598–605.CrossRefPubMedGoogle Scholar
  17. 17.
    Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29:4294–301.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, Spencer S, Harris J, Chung CH, Ang KK. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 2012;30:2102–11.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal MedicineYale University School of MedicineNew HavenUSA
  2. 2.Molecular Therapeutics ProgramFox Chase Cancer CenterPhiladelphiaUSA

Personalised recommendations