Emerging biomarkers in head and neck cancer in the era of genomics

Nature Reviews Clinical Oncology

Volumn 12, Issue 1, 2015, Pages 11-26

  Kang, Hyunseok ^a   Kiess, Ana ^a   Chung, Christine H ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN D1; EPIDERMAL GROWTH FACTOR RECEPTOR; FIBROBLAST GROWTH FACTOR RECEPTOR; NOTCH1 RECEPTOR; SCATTER FACTOR RECEPTOR; TUMOR MARKER; EGFR PROTEIN, HUMAN;

CANCER LOCALIZATION; CANCER PROGNOSIS; CLINICAL FEATURE; COPY NUMBER VARIATION; CYCLIN D1 GENE; DNA DETERMINATION; EGFR GENE; EPSTEIN BARR VIRUS; FGFR GENE; GAIN OF FUNCTION MUTATION; GENE EXPRESSION PROFILING; GENOME ANALYSIS; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HISTOPATHOLOGY; HUMAN; HYPOPHARYNX CANCER; HYPOXIA; LARYNX CANCER; MET GENE; MOUTH CANCER; MUTATIONAL ANALYSIS; NASOPHARYNX CARCINOMA; NONHUMAN; NOTCH1 GENE; ONCOGENE; OROPHARYNX CANCER; OVERALL SURVIVAL; PIK3CA GENE; POSITRON EMISSION TOMOGRAPHY; PREDICTIVE VALUE; PRIORITY JOURNAL; RADIOSENSITIVITY; REVIEW; SENSITIVITY AND SPECIFICITY; TUMOR BIOPSY; TUMOR SUPPRESSOR GENE; VIRUS DETECTION; WART VIRUS; EPSTEIN BARR VIRUS INFECTION; GENETICS; GENOMICS; HEAD AND NECK TUMOR; HUMAN PAPILLOMAVIRUS TYPE 16; NASOPHARYNX TUMOR; PAPILLOMAVIRUS INFECTION; PATHOLOGY; PERSONALIZED MEDICINE; PROGNOSIS; SQUAMOUS CELL CARCINOMA; VIROLOGY;

CARCINOMA, SQUAMOUS CELL; EPSTEIN-BARR VIRUS INFECTIONS; GENOMICS; HEAD AND NECK NEOPLASMS; HERPESVIRUS 4, HUMAN; HUMAN PAPILLOMAVIRUS 16; HUMANS; INDIVIDUALIZED MEDICINE; NASOPHARYNGEAL NEOPLASMS; PAPILLOMAVIRUS INFECTIONS; POSITRON-EMISSION TOMOGRAPHY; PROGNOSIS; RECEPTOR, EPIDERMAL GROWTH FACTOR; TUMOR MARKERS, BIOLOGICAL;

EID: 84927177309     PISSN: 17594774     EISSN: 17594782     Source Type: Journal    
DOI: 10.1038/nrclinonc.2014.192     Document Type: Review

References (203)

1. Pai, S. I. &Westra, W. H. Molecular pathology of head and neck cancer: implications for diagnosis, prognosis, and treatment. Annu. Rev. Pathol. 4, 49-70 (2009).
2. Laurie, S. A. &Licitra, L. Systemic therapy in the palliative management of advanced salivary gland cancers. J. Clin. Oncol. 24, 2673-2678 (2006).
3. Menefee, M. E., Smallridge, R. C. &Bible, K. C. Systemic therapeutic approaches to advanced thyroid cancers. Am. Soc. Clin. Oncol. Educ. Book 2012, 389-392 (2012).
4. National Cancer Institute. NCI Dictionary of Cancer Terms [online], http://www.cancer.gov/dictionary (2014).
5. Kern, S. E. Why your new cancer biomarker may never work: recurrent patterns and remarkable diversity in biomarker failures. Cancer Res. 72, 6097-6101 (2012).
6. Diamandis, E. P. The failure of protein cancer biomarkers to reach the clinic: why, and what can be done to address the problem? BMC Med. 10, 87 (2012).
7. Lo, K. W., To, K. F. &Huang, D. P. Focus on nasopharyngeal carcinoma. Cancer Cell 5, 423-428 (2004).
8. Shanmugaratnam, K. &Sobin, L. H. Histology Typing of Tumours of the Upper Respiratory Tract and Ear (Springer-Verlag, 1991).
9. Raab-Traub, N. Epstein-Barr virus in the pathogenesis of NPC. Semin. Cancer Biol. 12, 431-441 (2002).
10. Gourzones, C., Busson, P. &Raab-Traub, N. in Nasopharyngeal Carcinoma: Keys for Translational Medicine and Biology (ed. Busson, P.) 42-60 (Landes Bioscience/Springer Science and Business Media, 2013).
11. Slebos, R. J. et al. Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma. Clin. Cancer Res. 12, 701-709 (2006).
12. Stransky, N. et al. The mutational landscape of head and neck squamous cell carcinoma. Science 333, 1157-1160 (2011).
13. Agrawal, N. et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333, 1154-1157 (2011).
14. Chung, C. H., Bagheri, A. &D'Souza, G. Epidemiology of oral human papillomavirus infection. Oral Oncol. 50, 364-369 (2014).
15. Ang, K. K. et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N. Engl. J. Med. 363, 24-35 (2010).
16. Chung, C. H. et al. p16 protein expression and human papillomavirus status as prognostic biomarkers of non-oropharyngeal head and neck squamous cell carcinoma. J. Clin. Oncol. http://dx.doi.org/10.1200/JCO.2013.54.5228 (2014).
17. Kreimer, A. R., Clifford, G. M., Boyle, P. &Franceschi, S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol. Biomarkers Prev. 14, 467-475 (2005).
18. McLaughlin-Drubin, M. E. &Münger, K. Oncogenic activities of human papillomaviruses. Virus Res. 143, 195-208 (2009).
19. Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J. &Howley, P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63, 1129-1136 (1990).
20. Dyson, N., Howley, P. M., Münger, K. &Harlow, E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243, 934-937 (1989).
21. Rampias, T., Sasaki, C., Weinberger, P. &Psyrri, A. E6 and E7 gene silencing and transformed phenotype of human papillomavirus 16-positive oropharyngeal cancer cells. J. Natl Cancer Inst. 101, 412-423 (2009).
22. Leemans, C. R., Braakhuis, B. J. &Brakenhoff, R. H. The molecular biology of head and neck cancer. Nat. Rev. Cancer 11, 9-22 (2011).
23. Mellin Dahlstrand, H. et al. p16INK4a correlates to human papillomavirus presence, response to radiotherapy and clinical outcome in tonsillar carcinoma. Anticancer Res. 25, 4375-4383 (2005).
24. Weinberger, P. M. et al. Molecular classification identifies a subset of human papillomavirus-Associated oropharyngeal cancers with favorable prognosis. J. Clin. Oncol. 24, 736-747 (2006).
25. Jordan, R. C. et al. Validation of methods for oropharyngeal cancer HPV status determination in US Cooperative Group trials. Am. J. Surg. Pathol. 36, 945-954 (2012).
26. Lingen, M. W. et al. Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol. 49, 1-8 (2013).
27. Marur, S., D'Souza, G., Westra, W. H. &Forastiere, A. A. HPV-Associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 11, 781-789 (2010).
28. Quon, H. &Richmon, J. D. Treatment deintensification strategies for HPV-Associated head and neck carcinomas. Otolaryngol. Clin. North Am. 45, 845-861 (2012).
29. Fortin, A., Wang, C. S. &Vigneault, E. Influence of smoking and alcohol drinking behaviors on treatment outcomes of patients with squamous cell carcinomas of the head and neck. Int. J. Radiat. Oncol. Biol. Phys. 74, 1062-1069 (2009).
30. Chen, A. M. et al. Tobacco smoking during radiation therapy for head-And-neck cancer is associated with unfavorable outcome. Int. J. Radiat. Oncol. Biol. Phys. 79, 414-419 (2011).
31. Gillison, M. L. et al. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J. Clin. Oncol. 30, 2102-2111 (2012).
32. Maier, H., Dietz, A., Gewelke, U., Heller, W. D. &Weidauer, H. Tobacco and alcohol and the risk of head and neck cancer. Clin. Investig. 70, 320-327 (1992).
33. Goldenberg, D. et al. Habitual risk factors for head and neck cancer. Otolaryngol. Head Neck Surg. 131, 986-993 (2004).
34. Kutler, D. I. et al. High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Arch. Otolaryngol. Head Neck Surg. 129, 106-112 (2003).
35. Fakhry, C. et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J. Natl Cancer Inst. 100, 261-269 (2008).
36. Posner, M. R. et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann. Oncol. 22, 1071-1077 (2011).
37. Haddad, R. et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 14, 257-264 (2013).
38. Cohen, E. E. et al. DeCIDE: A phase III randomized trial of docetaxel(D), cisplatin (P), 5-fluorouracil (F) (TPF) induction chemotherapy in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck [abstract]. J. Clin. Oncol. 30 (Suppl.), a5500 (2012).
39. Ang, K. K. et al. A randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck carcinoma: RTOG 0522. J. Clin. Oncol. http://dx.doi.org/10.1200/JCO.2013.53.5633 (2014).
40. Lo, Y. M. et al. Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res. 59, 1188-1191 (1999).
41. Lo, Y. M. et al. Molecular prognostication of nasopharyngeal carcinoma by quantitative analysis of circulating Epstein-Barr virus DNA. Cancer Res. 60, 6878-6881 (2000).
42. Chan, A. T. et al. Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J. Natl Cancer Inst. 94, 1614-1619 (2002).
43. Lin, J. C. et al. Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N. Engl. J. Med. 350, 2461-2470 (2004).
44. Chan, A. T. et al. Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA. J. Clin. Oncol. 22, 3053-3060 (2004).
45. US National Library of Medicine. ClinicalTrials.gov [online], http://clinicaltrials.gov/ct2/show/NCT02135042 (2014).
46. Le, Q. T. et al. An international collaboration to harmonize the quantitative plasma Epstein-Barr virus DNA assay for future biomarker-guided trials in nasopharyngeal carcinoma. Clin. Cancer Res. 19, 2208-2215 (2013).
47. Leung, S. F. et al. Improved accuracy of detection of nasopharyngeal carcinoma by combined application of circulating Epstein-Barr virus DNA and anti-Epstein-Barr viral capsid antigen IgA antibody. Clin. Chem. 50, 339-345 (2004).
48. Ho, H. C., Ng, M. H., Kwan, H. C. &Chau, J. C. Epstein-Barr-virus-specific IgA and IgG serum antibodies in nasopharyngeal carcinoma. Br. J. Cancer 34, 655-660 (1976).
49. de-Vathaire, F. et al. Prognostic value of EBV markers in the clinical management of nasopharyngeal carcinoma (NPC): a multicenter follow-up study. Int. J. Cancer 42, 176-181 (1988).
50. Zong, Y. S. et al. Immunoglobulin A against viral capsid antigen of Epstein-Barr virus and indirect mirror examination of the nasopharynx in the detection of asymptomatic nasopharyngeal carcinoma. Cancer 69, 3-7 (1992).
51. Rischin, D. et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J. Clin. Oncol. 28, 4142-4148 (2010).
52. Lassen, P. et al. The influence of HPV-Associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: evaluation of the randomised DAHANCA 6&7 trial. Radiother. Oncol. 100, 49-55 (2011).
53. Fakhry, C. et al. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J. Clin. Oncol. 32, 3365-3373 (2014).
54. Huber, H. E., Goodhart, P. J. &Huang, P. S. Retinoblastoma protein reverses DNA bending by transcription factor E2F. J. Biol. Chem. 269, 6999-7005 (1994).
55. Montebugnoli, L. et al. Immunohistochemical expression of p16INK4A protein as a helpful marker of a subset of potentially malignant oral epithelial lesions: study on a series with long-term follow-up. Histopathology 57, 528-534 (2010).
56. Queiroz, A. B. et al. Expression of p27, p21WAF/Cip1, and p16INK4a in normal oral epithelium, oral squamous papilloma, and oral squamous cell carcinoma. Anticancer Res. 30, 2799-2803 (2010).
57. Lewis, J. S. Jr et al. Partial p16 staining in oropharyngeal squamous cell carcinoma: extent and pattern correlate with human papillomavirus RNA status. Mod. Pathol. 25, 1212-1220 (2012).
58. Reed, A. L. et al. High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res. 56, 3630-3633 (1996).
59. Hayes, D. N., Grandis, J. R. &El-Naggar, A. K. The Cancer Genome Atlas: integrated analysis of genome alterations in squamous cell carcinoma of the head and neck [abstract]. J. Clin. Oncol. 31 (Suppl.), a6009 (2013).
60. Westra, W. H. Detection of human papillomavirus in clinical samples. Otolaryngol. Clin. North Am. 45, 765-777 (2012).
61. Bishop, J. A. et al. Human papillomavirus-related carcinomas of the sinonasal tract. Am. J. Surg. Pathol. 37, 185-192 (2012).
62. Schache, A. G. et al. Validation of a novel diagnostic standard in HPV-positive oropharyngeal squamous cell carcinoma. Br. J. Cancer 108, 1332-1339 (2013).
63. Paidpally, V. et al. FDG-PET/CT imaging biomarkers in head and neck squamous cell carcinoma. Imaging Med. 4, 633-647 (2012).
64. Xie, P. et al. 18F-FDG PET or PET-CT to evaluate prognosis for head and neck cancer: a meta-Analysis. J. Cancer Res. Clin. Oncol. 137, 1085-1093 (2011).
65. Zhang, B., Li, X. &Lu, X. Standardized uptake value is of prognostic value for outcome in head and neck squamous cell carcinoma. Acta Otolaryngol. 130, 756-762 (2010).
66. Gupta, T. et al. Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-Analysis. Eur. J. Nucl. Med. Mol. Imaging 38, 2083-2095 (2011).
67. Schöder, H., Fury, M., Lee, N. &Kraus, D. PET monitoring of therapy response in head and neck squamous cell carcinoma. J. Nucl. Med. 50 (Suppl. 1), 74S-88S (2009).
68. Ong, S. C. et al. Clinical utility of 18F-FDG PET/CT in assessing the neck after concurrent chemoradiotherapy for locoregional advanced head and neck cancer. J. Nucl. Med. 49, 532-540 (2008).
69. Yao, M. et al. The role of FDG PET in management of neck metastasis from head-And-neck cancer after definitive radiation treatment. Int. J. Radiat. Oncol. Biol. Phys. 63, 991-999 (2005).
70. Porceddu, S. V. et al. Utility of positron emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer. Head Neck 27, 175-181 (2005).
71. Loo, S. W. et al. Neck dissection can be avoided after sequential chemoradiotherapy and negative post-treatment positron emission tomography-computed tomography in N2 head and neck squamous cell carcinoma. Clin. Oncol. (R. Coll. Radiol.) 23, 512-517 (2011).
72. Nayak, J. V. et al. Deferring planned neck dissection following chemoradiation for stage IV head and neck cancer: the utility of PET-CT. Laryngoscope 117, 2129-2134 (2007).
73. Vainshtein, J. M. et al. Reliability of post-chemoradiotherapy F-18-FDG PET/CT for prediction of locoregional failure in human papillomavirus-Associated oropharyngeal cancer. Oral Oncol. 50, 234-239 (2014).
74. Koshkareva, Y., Branstetter, B. F. 4th, Gaughan, J. P. &Ferris, R. L. Predictive accuracy of first posttreatment PET/CT in HPV-related oropharyngeal squamous cell carcinoma. Laryngoscope 124, 1843-1847 (2014).
75. Chan, J. Y. et al. Retrospective review of positron emission tomography with contrast-enhanced computed tomography in the posttreatment setting in human papillomavirus-Associated oropharyngeal carcinoma. Arch. Otolaryngol. Head Neck Surg. 138, 1040-1046 (2012).
76. Yao, M. et al. Clinical significance of postradiotherapy [18F]-fluorodeoxyglucose positron emission tomography imaging in management of head-And-neck cancer-A long-term outcome report. Int. J. Radiat. Oncol. Biol. Phys. 74, 9-14 (2009).
77. Lee, J. C. et al. F-18 FDG-PET as a routine surveillance tool for the detection of recurrent head and neck squamous cell carcinoma. Oral Oncol. 43, 686-692 (2007).
78. Brun, E. et al. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck 24, 127-135 (2002).
79. Menda, Y. et al. Kinetic analysis of 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) in head and neck cancer patients before and early after initiation of chemoradiation therapy. J. Nucl. Med. 50, 1028-1035 (2009).
80. Kandoth, C. et al. Mutational landscape and significance across 12 major cancer types. Nature 502, 333-339 (2013).
81. Seiwert, T. Y. et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin. Cancer Res. http://dx.doi.org/10.1158/1078-0432.CCR-13-3310 (2014).
82. Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546-1558 (2013).
83. National Cancer Institute. The Cancer Genome Atlas [online], http://cancergenome.nih.gov (2014).
84. Memorial Sloan Kettering Cancer Center. cBioPortal for Cancer Genomics [online], http://www.cbioportal.org/public-portal/(2014).
85. Sewell, A. et al. Reverse-phase protein array profiling of oropharyngeal cancer and significance of PIK3CA mutations in HPV-Associated head and neck cancer. Clin. Cancer Res. 20, 2300-2311 (2014).
86. Vermorken, J. B. et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 14, 697-710 (2013).
87. Vermorken, J. B. et al. Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial. Ann. Oncol. 25, 801-807 (2014).
88. Chong, C. R. &Janne, P. A. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat. Med. 19, 1389-1400 (2013).
89. Grandis, J. R. &Tweardy, D. J. TGF-Alpha and EGFR in head and neck cancer. J. Cell. Biochem. Suppl. 17F, 188-191 (1993).
90. Grandis, J. et al. Levels of TGF-α and EGFR protein in head and neck squamous cell carcinoma and patient survival. J. Natl Cancer Inst. 90, 824-832 (1998).
91. Ang, K. K. 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. 62, 7350-7356 (2002).
92. Keren, S., Shoude, Z., Lu, Z. &Beibei, Y. Role of EGFR as a prognostic factor for survival in head and neck cancer: a meta-Analysis. Tumour Biol. 35, 2285-2295 (2014).
93. Riesterer, O., Milas, L. &Ang, K. K. Use of molecular biomarkers for predicting the response to radiotherapy with or without chemotherapy. J. Clin. Oncol. 25, 4075-4083 (2007).
94. Burtness, B., Bauman, J. E. &Galloway, T. Novel targets in HPV-negative head and neck cancer: overcoming resistance to EGFR inhibition. Lancet Oncol. 14, e302-e309 (2013).
95. Chung, C. H. et al. Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J. Clin. Oncol. 24, 4170-4176 (2006).
96. Sok, J. C. et al. Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin. Cancer Res. 12, 5064-5073 (2006).
97. Turner, N. &Grose, R. Fibroblast growth factor signalling: from development to cancer. Nat. Rev. Cancer 10, 116-129 (2010).
98. Wiedemann, M. &Trueb, B. Characterization of a novel protein (FGFRL1) from human cartilage related to FGF receptors. Genomics 69, 275-279 (2000).
99. Walter, V. et al. Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes. PLoS ONE 8, e56823 (2013).
100. Malchers, F. et al. Cell-Autonomous and non-cell-Autonomous mechanisms of transformation by amplified FGFR1 in lung cancer. Cancer Discov. 4, 246-257 (2014).
101. Marshall, M. E. et al. Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells. Clin. Cancer Res. 17, 5016-5025 (2011).
102. Nguyen, P. T. et al. The FGFR1 inhibitor PD173074 induces mesenchymal-epithelial transition through the transcription factor AP-1. Br. J. Cancer 109, 2248-2258 (2013).
103. Sweeny, L. et al. Inhibition of fibroblasts reduced head and neck cancer growth by targeting fibroblast growth factor receptor. Laryngoscope 122, 1539-1544 (2012).
104. Peruzzi, B. &Bottaro, D. P. Targeting the c-Met signaling pathway in cancer. Clin. Cancer Res. 12, 3657-3660 (2006).
105. Seiwert, T. Y. et al. The MET receptor tyrosine kinase is a potential novel therapeutic target for head and neck squamous cell carcinoma. Cancer Res. 69, 3021-3031 (2009).
106. Knowles, L. M. et al. HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer. Clin. Cancer Res. 15, 3740-3750 (2009).
107. Ghadjar, P. et al. MET Y1253D-Activating point mutation and development of distant metastasis in advanced head and neck cancers. Clin. Exp. Metastasis 26, 1809-1815 (2009).
108. Engelman, J. A. et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039-1043 (2007).
109. Ewen, M. E. &Lamb, J. The activities of cyclin D1 that drive tumorigenesis. Trends Mol. Med. 10, 158-162 (2004).
110. Lannin, D. R. et al. Influence of socioeconomic and cultural factors on racial differences in late-stage presentation of breast cancer. JAMA 279, 1801-1807 (1998).
111. Kalish, L. H. et al. Deregulated cyclin D1 expression is associated with decreased efficacy of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in head and neck squamous cell carcinoma cell lines. Clin. Cancer Res. 10, 7764-7774 (2004).
112. Namazie, A. et al. Cyclin D1 amplification and p16(MTS1/CDK4I) deletion correlate with poor prognosis in head and neck tumors. Laryngoscope 112, 472-481 (2002).
113. Dhand, R. et al. PI 3-kinase: structural and functional analysis of intersubunit interactions. EMBO J. 13, 511-521 (1994).
114. Dhand, R. et al. PI 3-kinase is a dual specificity enzyme: autoregulation by an intrinsic protein-serine kinase activity. EMBO J. 13, 522-533 (1994).
115. Foukas, L. C., Beeton, C. A., Jensen, J., Phillips, W. A. &Shepherd, P. R. Regulation of phosphoinositide 3-kinase by its intrinsic serine kinase activity in vivo. Mol. Cell. Biol. 24, 966-975 (2004).
116. Kang, S., Denley, A., Vanhaesebroeck, B. &Vogt, P. K. Oncogenic transformation induced by the p110?, -?, and -? isoforms of class I phosphoinositide 3-kinase. Proc. Natl Acad. Sci. USA 103, 1289-1294 (2006).
117. Lee, J. Y., Engelman, J. A. & Cantley, L. C. Biochemistry. PI3K charges ahead. Science 317, 206-207 (2007).
118. Clarke, P. A. &Workman, P. Phosphatidylinositide-3-kinase inhibitors: addressing questions of isoform selectivity and pharmacodynamic/predictive biomarkers in early clinical trials. J. Clin. Oncol. 30, 331-333 (2012).
119. Lui, V. W. et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 3, 761-769 (2013).
120. Barbareschi, M. et al. Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin. Cancer Res. 13, 6064-6069 (2007).
121. Shen, D. et al. Dual fluorescent molecular substrates selectively report the activation, sustainability and reversibility of cellular PKB/Akt activity. Sci. Rep. 3, 1697 (2013).
122. Vousden, K. H. &Lane, D. P. p53 in health and disease. Nat. Rev. Mol. Cell Biol. 8, 275-283 (2007).
123. Haupt, Y., Maya, R., Kazaz, A. &Oren, M. Mdm2 promotes the rapid degradation of p53. Nature 387, 296-299 (1997).
124. Petitjean, A., Achatz, M. I., Borresen-Dale, A. L., Hainaut, P. &Olivier, M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 26, 2157-2165 (2007).
125. Brosh, R. &Rotter, V. When mutants gain new powers: news from the mutant p53 field. Nat. Rev. Cancer 9, 701-713 (2009).
126. Rodrigues, N. R. et al. p53 mutations in colorectal cancer. Proc. Natl Acad. Sci. USA 87, 7555-7559 (1990).
127. Milner, J. &Medcalf, E. A. Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell 65, 765-774 (1991).
128. Nylander, K., Dabelsteen, E. &Hall, P. A. The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck. J. Oral Pathol. Med. 29, 413-425 (2000).
129. Poeta, M. L. et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 357, 2552-2561 (2007).
130. Lindenbergh-van der Plas, M. et al. Prognostic significance of truncating TP53 mutations in head and neck squamous cell carcinoma. Clin. Cancer Res. 17, 3733-3741 (2011).
131. Licitra, L. et al. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J. Clin. Oncol. 24, 5630-5636 (2006).
132. Moser, R. et al. Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin. Cancer Res. 20, 4274-4288 (2014).
133. Bolos, V., Grego-Bessa, J. &de la Pompa, J. L. Notch signaling in development and cancer. Endocr. Rev. 28, 339-363 (2007).
134. Struhl, G. &Adachi, A. Nuclear access and action of notch in vivo. Cell 93, 649-660 (1998).
135. Song, X. et al. Common and complex Notch1 mutations in Chinese oral squamous cell carcinoma. Clin. Cancer Res. 20, 701-710 (2014).
136. Sun, W. et al. Activation of the NOTCH pathway in head and neck cancer. Cancer Res. 74, 1091-1104 (2014).
137. Chung, C. H. et al. Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell 5, 489-500 (2004).
138. Kumar, B. et al. EGFR, p16, HPV titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J. Clin. Oncol. 26, 3128-3137 (2008).
139. Keck, M. K. et al. Genomic profiling of kinase genes in head and neck squamous cell carcinomas to identify potentially targetable genetic aberrations in FGFR1/2, DDR2, EPHA2, and PIK3CA [abstract]. J. Clin. Oncol. 31 (Suppl.), a6010 (2013).
140. De Cecco, L., Bossi, P., Locati, L., Canevari, S. &Licitra, L. Comprehensive gene expression meta-Analysis of head and neck squamous cell carcinoma microarray data defines a robust survival predictor. Ann. Oncol. 25, 1628-1635 (2014).
141. Lujambio, A. &Lowe, S. W. The microcosmos of cancer. Nature 482, 347-355 (2012).
142. Childs, G. et al. Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am. J. Pathol. 174, 736-745 (2009).
143. Hatakeyama, H. et al. Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma. PLoS ONE 5, e12702 (2010).
144. Howard, J. D. et al. miRNA array analysis determines miR-205 is overexpressed in head and neck squamous cell carcinoma and enhances cellular proliferation. J. Cancer Res. Ther. 1, 153-162 (2013).
145. Tran, N., O'Brien, C. J., Clark, J. &Rose, B. Potential role of micro-RNAs in head and neck tumorigenesis. Head Neck 32, 1099-1111 (2010).
146. Nordsmark, M. et al. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother. Oncol. 77, 18-24 (2005).
147. Semenza, G. L. HIF-1 and human disease: one highly involved factor. Genes Dev. 14, 1983-1991 (2000).
148. Koukourakis, M. I. et al. Endogenous markers of two separate hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial. J. Clin. Oncol. 24, 727-735 (2006).
149. Le, Q. T. et al. Validation of lysyl oxidase as a prognostic marker for metastasis and survival in head and neck squamous cell carcinoma: Radiation Therapy Oncology Group trial 90-03. J. Clin. Oncol. 27, 4281-4286 (2009).
150. Overgaard, J., Eriksen, J. G., Nordsmark, M., Alsner, J. &Horsman, M. R. Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial. Lancet Oncol. 6, 757-764 (2005).
151. Tang, X. et al. Overexpression of human papillomavirus type 16 oncoproteins enhances hypoxia-inducible factor 1? protein accumulation and vascular endothelial growth factor expression in human cervical carcinoma cells. Clin. Cancer Res. 13, 2568-2576 (2007).
152. Kong, C. S. et al. The relationship between human papillomavirus status and other molecular prognostic markers in head and neck squamous cell carcinomas. Int. J. Radiat. Oncol. Biol. Phys. 74, 553-561 (2009).
153. Lassen, P. et al. HPV-Associated p16-expression and response to hypoxic modification of radiotherapy in head and neck cancer. Radiother. Oncol. 94, 30-35 (2009).
154. Winter, S. C. et al. Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers. Cancer Res. 67, 3441-3449 (2007).
155. Rischin, D. et al. Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02. J. Clin. Oncol. 24, 2098-2104 (2006).
156. Eschrich, S. A. et al. A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int. J. Radiat. Oncol. Biol. Phys. 75, 489-496 (2009).
157. Gildener-Leapman, N., Ferris, R. L. &Bauman, J. E. Promising systemic immunotherapies in head and neck squamous cell carcinoma. Oral Oncol. 49, 1089-1096 (2013).
158. Lopez-Albaitero, A. et al. Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL. J. Immunol. 176, 3402-3409 (2006).
159. Strome, S. E. et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res. 63, 6501-6505 (2003).
160. Baruah, P. et al. Decreased levels of alternative co-stimulatory receptors OX40 and 4-1BB characterise T cells from head and neck cancer patients. Immunobiology 217, 669-675 (2012).
161. Gildener-Leapman, N., Lee, J. &Ferris, R. L. Tailored immunotherapy for HPV positive head and neck squamous cell cancer. Oral Oncol. 50, 780-784 (2014).
162. Westra, W. H. The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol. 3, 78-81 (2009).
163. Lyford-Pike, S. et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-Associated head and neck squamous cell carcinoma. Cancer Res. 73, 1733-1741 (2013).
164. Brahmer, J. R. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366, 2455-2465 (2012).
165. Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454 (2012).
166. Messina, J. L. et al. 12-chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy? Sci. Rep. 2, 765 (2012).
167. Saloura, V. et al. T cell-inflamed phenotype correlates with mesenchymal subtype, expression of PD-L1 and other immune checkpoints in head and neck cancer [abstract]. J. Clin. Oncol. 32 (Suppl.), a6009 (2014).
168. Seiwert, T. Y. et al. A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-Associated and non-HPV-Associated head and neck (H/N) cancer [abstract]. J. Clin. Oncol. 32 (Suppl.), a6011 (2014).
169. Wilson, N. S. et al. An Fc? receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell 19, 101-113 (2011).
170. Kohrt, H. E. et al. Targeting CD137 enhances the efficacy of cetuximab. J. Clin. Invest. 124, 2668-2682 (2014).
171. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT02110082?term=NCT02110082&rank=1 (2014).
172. Diaz, L. A. Jr &Bardelli, A. Liquid biopsies: genotyping circulating tumor DNA. J. Clin. Oncol. 32, 579-586 (2014).
173. Vogelstein, B. &Kinzler, K. W. Digital PCR. Proc. Natl Acad. Sci. USA 96, 9236-9241 (1999).
174. Forshew, T. et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci. Transl. Med. 4, 136ra68 (2012).
175. Liu, Q. &Sommer, S. S. Pyrophosphorolysis-Activated polymerization (PAP): application to allele-specific amplification. Biotechniques 29, 1072-1076 (2000).
176. Dressman, D., Yan, H., Traverso, G., Kinzler, K. W. &Vogelstein, B. Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations. Proc. Natl Acad. Sci. USA 100, 8817-8822 (2003).
177. Meyerson, M., Gabriel, S. &Getz, G. Advances in understanding cancer genomes through second-generation sequencing. Nat. Rev. Genet. 11, 685-696 (2010).
178. Bettegowda, C. et al. Detection of circulating tumor DNA in early-And late-stage human malignancies. Sci. Transl. Med. 6, 224ra24 (2014).
179. Wu, Y. et al. Isolation and analysis of rare cells in the blood of cancer patients using a negative depletion methodology. Methods 64, 169-182 (2013).
180. Tong, X., Yang, L., Lang, J. C., Zborowski, M. &Chalmers, J. J. Application of immunomagnetic cell enrichment in combination with RT-PCR for the detection of rare circulating head and neck tumor cells in human peripheral blood. Cytometry B Clin. Cytom. 72, 310-323 (2007).
181. Tinhofer, I., Hristozova, T., Stromberger, C., Keilhoiz, U. &Budach, V. Monitoring of circulating tumor cells and their expression of EGFR/phospho-EGFR during combined radiotherapy regimens in locally advanced squamous cell carcinoma of the head and neck. Int. J. Radiat. Oncol. Biol. Phys. 83, e685-e690 (2012).
182. Scheffner, M., Huibregtse, J. M., Vierstra, R. D. &Howley, P. M. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75, 495-505 (1993).
183. Huh, K. et al. Human papillomavirus type 16 E7 oncoprotein associates with the cullin 2 ubiquitin ligase complex, which contributes to degradation of the retinoblastoma tumor suppressor. J. Virol. 81, 9737-9747 (2007).
184. Harbour, J. W., Luo, R. X., Dei Santi, A., Postigo, A. A. &Dean, D. C. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 98, 859-869 (1999).
185. Rubin, S. M., Gall, A. L., Zheng, N. &Pavletich, N. P. Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release. Cell 123, 1093-1106 (2005).
186. Khleif, S. N. et al. Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc. Natl Acad. Sci. USA 93, 4350-4354 (1996).
187. Lynn, T. C., Tu, S. M. &Kawamura, A. Jr. Long-term follow-up of IgG and IgA antibodies against viral capsid antigens of Epstein-Barr virus in nasopharyngeal carcinoma. J. Laryngol. Otol. 99, 567-572 (1985).
188. Smeets, S. J. et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int. J. Cancer 121, 2465-2472 (2007).
189. Shi, W. et al. Comparative prognostic value of HPV16 E6 mRNA compared with in situ hybridization for human oropharyngeal squamous carcinoma. J. Clin. Oncol. 27, 6213-6221 (2009).
190. Schache, A. G. et al. Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination. Clin. Cancer Res. 17, 6262-6271 (2011).
191. Schlecht, N. F. et al. A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer. Mod. Pathol. 24, 1295-1305 (2011).
192. Rotnaglova, E. et al. HPV involvement in tonsillar cancer: prognostic significance and clinically relevant markers. Int. J. Cancer 129, 101-110 (2011).
193. Wong, R. J. et al. Diagnostic and prognostic value of [18F]fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma. J. Clin. Oncol. 20, 4199-4208 (2002).
194. Heinrich, M. C. et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol. 21, 4342-4349 (2003).
195. Kantarjian, H. et al. Survival advantage with imatinib mesylate therapy in chronic-phase chronic myelogenous leukemia (CML-CP) after IFN-Alpha failure and in late CML-CP, comparison with historical controls. Clin. Cancer Res. 10, 68-75 (2004).
196. Rosell, R. et al. Screening for epidermal growth factor receptor mutations in lung cancer. N. Engl. J. Med. 361, 958-967 (2009).
197. Shaw, A. T. et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 12, 1004-1012 (2011).
198. Chapman, P. B. et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364, 2507-2516 (2011).
199. Karapetis, C. S. et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med. 359, 1757-1765 (2008).
200. Coiffier, B. et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N. Engl. J. Med. 346, 235-242 (2002).
201. Schulz, H. et al. Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-Analysis. J. Natl Cancer Inst. 99, 706-714 (2007).
202. Bang, Y. J. et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376, 687-697 (2010).
203. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783-792 (2001).