• 1
    Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010; 60: 277-300.
  • 2
    The Catalogue of Somatic Mutations in Cancer (COSMIC) database. Available at: Accessed August 18, 2009.
  • 3
    Kwon H-C, Roh MS, Oh SY, et al. Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluoruracil/oxaliplatin chemotherapy in advanced gastric cancer. Ann Oncol. 2007; 18: 504-509.
  • 4
    Johnson SW, Perez RP, Godwin AK, et al. Role of platinum-DNA adduct formation and removal in cisplatin resistance in human ovarian cancer cell lines. Biochem Pharmacol. 1994; 47: 689-697.
  • 5
    Johnson SW, Swiggard PA, Handel LM, et al. Relationship between platinum-DNA adduct formation and removal and cisplatin cytotoxicity in cisplatin-sensitive and -resistant human ovarian cancer cells. Cancer Res. 1994; 54: 5911-5916.
  • 6
    Reed E. Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. Cancer Treat Rev. 1998; 24: 331-344.
  • 7
    Reardon JT, Vaisman A, Chaney SG, et al. Efficient nucleotide excision repair of cisplatin, oxaliplatin, and bis-aceto-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216) platinum intrastrand DNA diadducts. Cancer Res. 1999; 59: 3968-3971.
  • 8
    Zhen W, Link CJ Jr, O'Connor PM, et al. Increased gene-specific repair of cisplatin interstrand cross-links in cisplatin-resistant human ovarian cancer cell lines. Mol Cell Biol. 1992; 12: 3689-3698.
  • 9
    Bramson J, Panasci L. Effect of ERCC-1 overexpression on sensitivity of Chinese hamster ovary cells to DNA damaging agents. Cancer Res. 1993; 53: 3227-3240.
  • 10
    Jiang H, Yang L-Y. Cell cycle checkpoint abrogator UCN-01 inhibits DNA repair: association with attenuation of the interaction of XPA and ERCC1 nucleotide excision repair protein. Cancer Res. 1999; 59: 4529-4534.
  • 11
    Selvakumaran M, Pisarcik DA, Bao R, et al. Enhanced cisplatin cytotoxicity by disturbing the nucleotide excision repair pathway in ovarian cancer cell lines. Cancer Res. 2003; 63: 1311-1316.
  • 12
    Chang I-Y, Kim M-H, Kim HB, et al. Small interfering RNA-induced suppression of ERCC1 enhances sensitivity of human cancer cells to cisplatin. Biochem Biophys Res Comm. 2005; 327: 225-233.
  • 13
    Dabholkar M, Vionnet J, Bostick-Bruton F, et al. Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy. J Clin Invest. 1994; 94: 703-708.
  • 14
    Metzger R, Leichman CG, Danenberg KD, et al. ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol. 1998; 16: 309-316.
  • 15
    Shirota Y, Stoehlmacher J, Brabender J, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol. 2001; 19: 4298-4304.
  • 16
    Moore-Joshi M-B, Shirota Y, Danenberg KD, et al. High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer. Clin Cancer Res. 2005; 11: 2215-2221.
  • 17
    Lord RV, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002; 8: 2286-2291.
  • 18
    Ceppi P, Volante M, Novello S, et al. ERCC1 and RRM1 gene expression but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine. Ann Oncol. 2006; 17: 1818-1825.
  • 19
    Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006; 355: 893-891.
  • 20
    Bhagwat NR, Roginskaya VY, Acquafondata MB, et al. Immunodetection of DNA repair endonuclease ERCC1-XPF in human tissue. Cancer Res. 2009; 69: 6831-6838.
  • 21
    Cobo M, Isla D, Massuti B, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007; 25: 2747-2754.
  • 22
    Handra-Luca A, Hernandez J, Mountzios G, et al. Excision repair cross complementation group1 immunohistochemical expression predicts objective response and cancer-specific survival in patients treated with cisplatin-based induction chemotherapy for locally advanced head and neck squamous cell carcinoma. Clin Cancer Res. 2007; 13: 3855-3859.
  • 23
    Jun HJ, Ahn MJ, Kim HS, et al. ERCC1 expression as a predictive marker of squamous cell carcinoma of the head and neck treated with cisplatin-based concurrent chemoradiation. Br J Cancer. 2008; 99: 167-172.
  • 24
    Carles J, Monzo M, Amat M, et al. Single-nucleotide polymorphisms in base excision repair, nucleotide excision repair, and double strand break genes as markers for response to radiotherapy in patients with stage I to II head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2006; 66: 1022-1030.
  • 25
    Kwon WS, Rha SY, Choi YH, et al. Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines. Pharmacogenet Genomics. 2006; 16: 429-438.
  • 26
    Davidson JD, Ma L, Flagella M, et al. An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines. Cancer Res. 2004; 64: 3761-3766.
  • 27
    Goan Y-G, Zhou B, Hu E, et al. Overexpression of ribonucleotide reductase as a mechanism of resistance to 2,2-difluorodeoxycytidine in the human KB cancer cell line. Cancer Res. 1999; 59: 4204-4207.
  • 28
    Dumontet C, Fabianowska-Majewska K, Mantincic D, et al. Common resistance mechanisms to deoxynucleoside analogues in variants of the human erythroleukaemic line K562. Br J Haematol. 1999; 106: 78-85.
  • 29
    Bepler G, Kusmartseva I, Sharma S, et al. RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006; 24: 4731-4737.
  • 30
    Yeo W, Soong RC, Chuah BY, et al. Correlation of RRM1 promoter regions single nucleotide polymorphisms (SNPs) with response and outcome in breast cancer patients treated with gemcitabine-based chemotherapy [abstract]. J Clin Oncol. 2008; 26(suppl). Abstract 14513.
  • 31
    Rosell R, Danenberg KD, Alberola V, et al. Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin Cancer Res. 2004; 10: 1318-1325.
  • 32
    Papadaki C, Trypaki M, Koutsopoulos A, et al. Association of tumoral BRCA1, RRM1, and RRM2 mRNA expression levels with clinical response to front-line docetaxel/gemcitabine (DG) chemotherapy in patients with non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2008; 26(suppl). Abstract 8112.
  • 33
    Kavallaris M, Kuo DY, Burkhart CA, et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest. 1997; 100: 1282-1293.
  • 34
    Ranganathan S, Dexter DW, Benetatos CA, Hudes GR. Cloning and sequencing of human betaIII-tubulin cDNA: induction of betaIII isotype in human prostate carcinoma cells by acute exposure to antimicrotubule agents. Biochim Biophys Acta. 1998; 1395: 237-245.
  • 35
    Monzo M, Rosell R, Sanchez JJ, et al. Paclitaxel resistance in non-small-cell lung cancer associated with beta-tubulin gene mutations. J Clin Oncol. 1999; 17: 1786-1793.
  • 36
    Seve P, Mackey J, Isaac S, et al. Class III beta-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel. Mol Cancer Ther. 2005; 4: 2001-2007.
  • 37
    Dumontet C, Isaac S, Souquet PJ, et al. Expression of class III beta tubulin in non-small cell lung cancer is correlated with resistance to taxane chemotherapy. Bull Cancer. 2005; 92: E25-E30.
  • 38
    Cullen KJ, Schumaker L, Nikitakis N, et al. Beta-tubulin-II expression strongly predicts outcome in patients receiving induction chemotherapy for locally advanced squamous carcinoma of the head and neck: a companion analysis of the TAX 324 trial. J Clin Oncol. 2009; 27: 6222-6228.
  • 39
    Walboomers JM, Jabobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189: 12-19.
  • 40
    Chaturvedi A, Engels E, Anderson W, et al. Incidence trends for human papillomavirus-related (HPV-R) and unrelated (HPV-U) head and neck squamous cell carcinomas (HNSCC) in the United States (US) [abstract]. J Clin Oncol. 2007; 25(suppl). Abstract 6001.
  • 41
    Ryerson AB, Peters ES, Coughlin SS, et al. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003. Cancer. 2008; 113(10 suppl): 2901-2909.
  • 42
    Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010; 363: 24-35.
  • 43
    Herrero R, Castellsague X, Pawlita M, et al. Human papillomavirus and oral cancer: the International Agency for Research on Cancer Multicenter Study. J Natl Cancer Inst. 2003; 95: 1772-1783.
  • 44
    D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007; 356: 1944-1956.
  • 45
    Fakhry C, Westra WH, Li S, et al. Improved survival of patient with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008; 1000: 261-269.
  • 46
    Syrjanen S. Human papillomavirus (HPV) in head and neck cancer. J Clin Virol. 2005; 32S: S59-S66.
  • 47
    Pecoraro G, Morgan D, Defendi V. Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells. Proc Natl Acad Sci U S A. 1989; 86: 563-567.
  • 48
    Park NH, Min BM, Li SL, et al. Immortalization of normal human oral keratinocytes with type 16 human papillomavirus. Carcinogenesis. 1991; 12: 1627-1631.
  • 49
    Andl T, Kahn T, Pfuhl A, et al. Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res. 1998; 58: 5-13.
  • 50
    Mork J, Lie AK, Glattre E, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001; 344: 1125-1131.
  • 51
    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: 709-720.
  • 52
    Rischin D, Young R, Fisher R, 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. 2010; 28: 4142-4148.
  • 53
    Gillison ML, Zhang Q, Ang K, et al. Analysis of the effect of p16 and tobacco pack-years (p-y) on overall (OS) and progression-free survival (PFS) for patients with oropharynx cancer (OPC) in Radiation Therapy Oncology Group (RTOG) protocol 9003 [abstract]. J Clin Oncol. 2010; 28: (15 suppl). Abstract 5510.
  • 54
    Lorch J, Posner M, Goloubeva O, et al. Five-year survival (OS) and patterns of failure for human papillomavirus (HPV) positive and negative oropharynx cancer (OPC) in the TAX 324 clinical trial: results of sequential therapy [abstract]. Ann Oncol. 2010; 21(suppl 8). Abstract 1004O.
  • 55
    Center for Disease Control and Prevention. Human papillomavirus: HPV information for clinicians. April 2007. Available at: Accessed August 18, 2009.
  • 56
    Kirnbauer R, Hubbert NL, Wheeler CM, et al. A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Natl Cancer Inst. 1994; 86: 494-499.
  • 57
    Ang KK, Zhang QE, Rosenthal DI, et al. Phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab (Cetz) for locally-advanced HNSCC [abstract]. J Clin Oncol. 2011; 29(suppl). Abstract 5500.
  • 58
    Williams HK. Molecular pathogenesis of oral squamous carcinoma. Mol Pathol. 2000; 53: 165-172.
  • 59
    Khambata-Ford S, Garrett CR, Meropol NJ, et al. Expression of epiregulin and amphiregulin and K-RAS mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007; 25: 3230-3237.
  • 60
    Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-RAS mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359: 1757-1765.
  • 61
    Bokemeyer C, Bondarenko I, Hartmann JT, et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: the OPUS experience [abstract]. J Clin Oncol. 2008; 26(suppl). Abstract 4000.
  • 62
    Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patient with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009; 27: 2091-2096.
  • 63
    European Medicines Agency. Summary of product characteristics. Available at: Accessed on October 1, 2010.
  • 64
    Rathcke IO, Gottschlich S, Gorogh T, et al. Incidence of point mutations in Ki-ras codon 12 and 13 in squamous epithelial carcinomas of the head-neck region. Laryngorhinootologie. 1996; 75: 465-470.
  • 65
    Yarbrough WG, Shores C, Witsell DL, et al. Ras mutations and expression in head and neck squamous cell carcinomas. Laryngoscope. 1994; 104: 1337-1347.
  • 66
    Bissada E, Abou-Chacra Z, Weng X, et al. Prevalence of K-RAS codon 12 mutations in locally advanced head and neck squamous cell carcinoma and influence with regards to response to chemoradiation therapy [abstract]. J Clin Oncol. 2008; 26(suppl). Abstract 17005.
  • 67
    Hoa M, Davis SL, Ames SJ, et al. Amplification of wild-type K-RAS promotes growth of head and neck squamous cell carcinoma. Cancer Res. 2002; 62: 7154-7156.
  • 68
    Maurizi M, Almadori G, Ferradina G, et al. Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma. Br J Cancer. 1996;74:1253-1257.
  • 69
    Rubin Grandis J, Tweardy DJ. Elevated levels of transforming growth factor α and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res. 1993; 53: 3579-3584.
  • 70
    Dassonville O, Formento JL, Francoual M, et al. Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer. J Clin Oncol. 1993; 11: 1873-1878.
  • 71
    Ang KK, Berkey BA, Tu X, 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: 7350-7356.
  • 72
    Burtness B, Goldwasser MA, Flood W, et al. 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; 24: 8646-8654.
  • 73
    Atkins D, Reiffen K-A, Tegtmeier CL, et al. Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem. 2004; 52: 893-901.
  • 74
    Vermorken JB, Mesia R, Remenar E, et al. Predictors of efficacy in the EXTREME study: cetuximab plus platinum-based therapy first-line in patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) [abstract]. Ann Oncol. 2008; 19(suppl). Abstract 6870.
  • 75
    Psyrri A, Yu Z, Weinberger PM, et al. Quantitative determination of nuclear and cytoplasmic epidermal growth factor receptor expression in oropharyngeal squamous cell cancer by using automated quantitative analysis. Clin Cancer Res. 2005; 11: 5856-5862.
  • 76
    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: 5064-5073.
  • 77
    Loeffler-Ragg J, Witsch-Baumgartner M, Tzankov A, et al. Low incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma. Eur J Cancer. 2006; 42: 109-111.
  • 78
    Eberhard DA, Johnson BE, Amler LC, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005; 23: 5900-5909.
  • 79
    Lee JW, Soung YH, Kim SY, et al. Somatic mutations of EGFR gene in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2005; 11: 2879-2882.
  • 80
    Carbone DP, Seymour L, Ding K, et al. Serum proteomic prediction of outcomes in advanced NSCLC patients treated with erlotinib/placebo in the NCIC Clinical Trials Group BR. 21 trial [abstract]. J Thorac Oncol. 2010; 5(suppl 1). Abstract 203O.
  • 81
    Chung CH, Seeley EH, Roder H, et al. Detection of tumor epidermal growth factor receptor pathway dependence by serum mass spectrometry in cancer patients. Cancer Epidemiol Biomarkers Prev. 2010; 19: 358-365.
  • 82
    Byers LA, Holsinger FC, Kies MS, et al. Serum signature of hypoxia-regulated factors is associated with progression after induction therapy in head and neck squamous cell cancer. Mol Cancer Ther. 2010; 9: 1755-1763.
  • 83
    Ferris RL, Lee SC, Feinstein C, et al. Serum biomarkers as predictors of clinical outcome after cetuximab-based therapy in patients with locally-advanced squamous-cell carcinoma of the head and neck [abstract]. J Clin Oncol. 2009; 27(15 suppl). Abstract 6035.