Targeting pathways mediating resistance to anti-EGFR therapy in squamous cell carcinoma of the head and neck

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Head and Neck Cancers. Version 1. NCCN; 2015.
   Google Scholar
• Chaturvedi AK, Engels EA, Anderson WF, et al. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008;26(4):612–619.
   PubMed Web of Science ®Google Scholar
• Holbro T, Civenni G, Hynes NE. The ErbB receptors and their role in cancer progression. Exp Cell Res. 2003;284(1):99–110.
   PubMed Web of Science ®Google Scholar
• Ligand-induced SJ. Receptor-mediated dimerization and activation of EGF receptor. Cell. 2002;110(6):669–672.
   PubMed Web of Science ®Google Scholar
• Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127–137.
   PubMed Web of Science ®Google Scholar
• Arteaga CL. Epidermal growth factor receptor dependence in human tumors: more than just expression? Oncologist. 2002;7 Suppl 4:31–39.
   PubMed Web of Science ®Google Scholar
• Cruz JJ, Ocaña A, Del BE, et al. Targeting receptor tyrosine kinases and their signal transduction routes in head and neck cancer. Ann Oncol. 2007;18(3):421–430.
   PubMed Web of Science ®Google Scholar
• Grandal MV, Madshus IH. Epidermal growth factor receptor and cancer: control of oncogenic signalling by endocytosis. J Cell Mol Med. 2008;12(5A):1527–1534.
   PubMed Web of Science ®Google Scholar
• Thomas GR, Nadiminti H, Regalado J. Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int J Exp Pathol. 2005;86(6):347–363.
   PubMed Web of Science ®Google Scholar
• Rubin Grandis J, Melhem MF, Gooding WE, et al. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst. 1998;90(11):824–832.
   PubMed Web of Science ®Google Scholar
• 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(24):7350–7356.
   PubMed Web of Science ®Google Scholar
• 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(10):1873–1878.
   PubMed Web of Science ®Google Scholar
• Chung CH, Ely K, McGavran L, 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. 2006;24(25):4170–4176.
   PubMed Web of Science ®Google Scholar
• Temam S, Kawaguchi H, El-Naggar AK, et al. Epidermal growth factor receptor copy number alterations correlate with poor clinical outcome in patients with head and neck squamous cancer. J Clin Oncol. 2007;25(16):2164–2170.
   PubMed Web of Science ®Google Scholar
• Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–1127.
   PubMed Web of Science ®Google Scholar
• Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007;25(16):2171–2177.
   PubMed Web of Science ®Google Scholar
• Baselga J, Trigo JM, Bourhis J, et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005;23(24):5568–5577.
   PubMed Web of Science ®Google Scholar
• Herbst RS, Arquette M, Shin DM, et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol. 2005;23(24):5578–5587.
   PubMed Web of Science ®Google Scholar
• 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;23(34):8646–8654.
   PubMed Web of Science ®Google Scholar
• Vermorken JB, Stöhlmacher-Williams J, Davidenko I, 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. 2013;14(8):697–710.
   PubMed Web of Science ®Google Scholar
• Machiels J-P, Subramanian S, Ruzsa A, et al. Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial. Lancet Oncol. 2011;12(4):333–343.
   PubMed Web of Science ®Google Scholar
• Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(11):1864–1871.
   PubMed Web of Science ®Google Scholar
• Argiris A, Ghebremichael M, Gilbert J, et al. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013;31(11):1405–1414.
   PubMed Web of Science ®Google Scholar
• 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(6):567–578.
   PubMed Web of Science ®Google Scholar
• Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11(1):21–28.
   PubMed Web of Science ®Google Scholar
• Ang KK, Zhang Q, Rosenthal DI, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014;32(27):2940–2950.
   PubMed Web of Science ®Google Scholar
• Harrington KJ, Temam S, D’Cruz A, et al. Final analysis: a randomized, blinded, placebo (P)-controlled phase III study of adjuvant postoperative lapatinib (L) with concurrent chemotherapy and radiation therapy (CH-RT) in high-risk patients with squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol. 2014;32(5s):Abstract 6005.
   Google Scholar
• Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015;16(5):583–594.
   PubMed Web of Science ®Google Scholar
• ERBITUX^® (cetuximab) injection, for intravenous infusion [package insert]. Branchburg (NJ): ImClone LLC; 2013.
   Google Scholar
• Fakhry C, Westra WH, Li S, 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. 2008;100(4):261–269.
   PubMedGoogle Scholar
• Rosenthal DI, Harari PM, Giralt J, et al. Association of human papillomavirus and p16 status with outcomes in the IMCL-9815 phase III registration trial for patients with locoregionally advanced oropharyngeal squamous cell carcinoma of the head and neck treated with radiotherapy with or without cetuximab. J Clin Oncol. 2016;34(12):1300–1308.
   Web of Science ®Google Scholar
• Licitra L, Mesia R, Rivera F, et al. Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol. 2011;22(5):1078–1087.
   PubMed Web of Science ®Google Scholar
• Licitra L, Störkel S, Kerr KM, et al. Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer. 2013;49(6):1161–1168.
   PubMed Web of Science ®Google Scholar
• Morris ZS, Harari PM. Interaction of radiation therapy with molecular targeted agents. J Clin Oncol. 2014;32(26):2886–2893.
   PubMed Web of Science ®Google Scholar
• Yang XD, Jia XC, Corvalan JR, et al. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001;38(1):17–23.
   PubMed Web of Science ®Google Scholar
• Vermorken JB, Psyrri A, Mesía R, 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. 2014;25(4):801–807.
   PubMed Web of Science ®Google Scholar
• Schick U, Gujral DM, Richards TM, et al. Zalutumumab in head and neck cancer. Expert Opin Biol Ther. 2012;12(1):119–125.
   PubMed Web of Science ®Google Scholar
• Eriksen JG, Maare C, Johansen J, et al. DAHANCA 19: first results of a randomized phase III study of the importance of the EGFR-inhibitor zalutumumab for the outcome of primary curative radiotherapy for squamous cell carcinoma of the head and neck. Late breaking abstract presented at: the European Cancer Congress; September 27 – 2013 October 1; Amsterdam, Netherlands; 2013. Abstract 12.
   Google Scholar
• Ramakrishnan MS, Eswaraiah A, Crombet T, et al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs. 2009;1(1):41–48.
   PubMed Web of Science ®Google Scholar
• Rodríguez MO, Rivero TC, Del Castillo BR, et al. Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck. Cancer Biol Ther. 2010;9(5):343–349.
   PubMed Web of Science ®Google Scholar
• Basavaraj C, Sierra P, Shivu J, et al. Nimotuzumab with chemoradiation confers a survival advantage in treatment-naive head and neck tumors over expressing EGFR. Cancer Biol Ther. 2010;10(7):673–681.
   PubMed Web of Science ®Google Scholar
• Iannello A, Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev. 2005;24(4):487–499.
   PubMed Web of Science ®Google Scholar
• Dassonville O, Bozec A, Fischel JL, et al. EGFR targeting therapies: monoclonal antibodies versus tyrosine kinase inhibitors. Similarities and differences. Crit Rev Oncol Hematol. 2007;62(1):53–61.
   PubMed Web of Science ®Google Scholar
• López-Albaitero A, Ferris RL. Immune activation by epidermal growth factor receptor specific monoclonal antibody therapy for head and neck cancer. Arch Otolaryngol Head Neck Surg. 2007;133(12):1277–1281.
   PubMedGoogle Scholar
• Iressa^® (gefitinib tablets) [package insert]. Wilmington (DE): AstraZeneca Pharmaceuticals LP; 2005.
   Google Scholar
• Cohen EE, Rosen F, Stadler WM, et al. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2003;21(10):1980–1987.
   PubMed Web of Science ®Google Scholar
• Cohen EE, Haraf DJ, Kunnavakkam R, et al. Epidermal growth factor receptor inhibitor gefitinib added to chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol. 2010;28(20):3336–3343.
   PubMed Web of Science ®Google Scholar
• TARCEVA^® (erlotinib) tablets, for oral use [package insert]. South San Francisco (CA): Genentech; 2014.
   Google Scholar
• Martins RG, Parvathaneni U, Bauman JE, et al. Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: a randomized phase II trial. J Clin Oncol. 2013;31(11):1415–1421.
   PubMed Web of Science ®Google Scholar
• Erjala K, Sundvall M, Junttila TT, et al. Signaling via ErbB2 and ErbB3 associates with resistance and epidermal growth factor receptor (EGFR) amplification with sensitivity to EGFR inhibitor gefitinib in head and neck squamous cell carcinoma cells. Clin Cancer Res. 2006;12(13):4103–4111.
   PubMed Web of Science ®Google Scholar
• Yonesaka K, Zejnullahu K, Okamoto I, et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med. 2011;3(99):99ra86.
   PubMed Web of Science ®Google Scholar
• Cavalot A, Martone T, Roggero N, et al. Prognostic impact of HER-2/neu expression on squamous head and neck carcinomas. Head Neck. 2007;29(7):655–664.
   PubMed Web of Science ®Google Scholar
• Wheeler SE, Suzuki S, Thomas SM, et al. Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation. Oncogene. 2010;29(37):5135–5145.
   PubMed Web of Science ®Google Scholar
• 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(17):5064–5073.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–582.
   PubMed Web of Science ®Google Scholar
• Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157–1160.
   PubMed Web of Science ®Google Scholar
• Hammerman PS, Hayes DN, Grandis JR. Therapeutic insights from genomic studies of head and neck squamous cell carcinomas. Cancer Discov. 2015;5(3):239–244.
   PubMed Web of Science ®Google Scholar
• Zhang K, Wang D, Song J. Cortactin is involved in transforming growth factor-beta1-induced epithelial-mesenchymal transition in AML-12 cells. Acta Biochim Biophys Sin (Shanghai). 2009;41(10):839–845.
   PubMed Web of Science ®Google Scholar
• Timpson P, Wilson AS, Lehrbach GM, et al. Aberrant expression of cortactin in head and neck squamous cell carcinoma cells is associated with enhanced cell proliferation and resistance to the epidermal growth factor receptor inhibitor gefitinib. Cancer Res. 2007;67(19):9304–9314.
   PubMed Web of Science ®Google Scholar
• Haddad Y, Choi W, McConkey DJ. Delta-crystallin enhancer binding factor 1 controls the epithelial to mesenchymal transition phenotype and resistance to the epidermal growth factor receptor inhibitor erlotinib in human head and neck squamous cell carcinoma lines. Clin Cancer Res. 2009;15(2):532–542.
   PubMed Web of Science ®Google Scholar
• Shien K, Toyooka S, Yamamoto H, et al. Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells. Cancer Res. 2013;73(10):3051–3061.
   PubMed Web of Science ®Google Scholar
• Wilson C, Nicholes K, Bustos D, et al. Overcoming EMT-associated resistance to anti-cancer drugs via Src/FAK pathway inhibition. Oncotarget. 2014;5(17):7328–7341.
   PubMed Web of Science ®Google Scholar
• Byers LA, Diao L, Wang J, et al. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res. 2013;19(1):279–290.
   PubMed Web of Science ®Google Scholar
• Lau PC, Chan AT. Novel therapeutic target for head and neck squamous cell carcinoma: HGF-MET signaling pathway. Anticancer Drugs. 2011;22(7):665–673.
   PubMed Web of Science ®Google Scholar
• Xu H, Stabile LP, Gubish CT, et al. Dual blockade of EGFR and c-Met abrogates redundant signaling and proliferation in head and neck carcinoma cells. Clin Cancer Res. 2011;17(13):4425–4438.
   PubMed Web of Science ®Google Scholar
• Viloria-Petit A, Crombet T, Jothy S, et al. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res. 2001;61(13):5090–5101.
   PubMed Web of Science ®Google Scholar
• Jameson MJ, Beckler AD, Taniguchi LE, et al. Activation of the insulin-like growth factor-1 receptor induces resistance to epidermal growth factor receptor antagonism in head and neck squamous carcinoma cells. Mol Cancer Ther. 2011;10(11):2124–2134.
   PubMed Web of Science ®Google Scholar
• Kalish LH, Kwong RA, Cole IE, 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. 2004;10(22):7764–7774.
   PubMed Web of Science ®Google Scholar
• Rebucci M, Peixoto P, Dewitte A, et al. Mechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance. Int J Oncol. 2011;38(1):189–200.
   PubMed Web of Science ®Google Scholar
• Agrawal N, Frederick MJ, Pickering CR, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333(6046):1154–1157.
   PubMed Web of Science ®Google Scholar
• Qiu W, Schonleben F, Li X, et al. PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res. 2006;12(5):1441–1446.
   PubMed Web of Science ®Google Scholar
• Lui VW, Hedberg ML, Li H, et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 2013;3(7):761–769.
   PubMed Web of Science ®Google Scholar
• Keck MK, Zuo Z, Khattri A, 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. J Clin Oncol. 2013;31:Abstract 6010.
   Google Scholar
• Jimeno A, Kulesza P, Wheelhouse J, et al. Dual EGFR and mTOR targeting in squamous cell carcinoma models, and development of early markers of efficacy. Br J Cancer. 2007;96(6):952–959.
   PubMed Web of Science ®Google Scholar
• Wheeler DL, Iida M, Kruser TJ, et al. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab. Cancer Biol Ther. 2009;8(8):696–703.
   PubMed Web of Science ®Google Scholar
• TYKERB^® (lapatinib) tablets [package insert]. Research Triangle Park (NC): GlaxoSmithKline; 2012.
   Google Scholar
• Del Campo JM, Hitt R, Sebastian P, et al. Effects of lapatinib monotherapy: results of a randomised phase II study in therapy-naive patients with locally advanced squamous cell carcinoma of the head and neck. Br J Cancer. 2011;105(5):618–627.
   PubMed Web of Science ®Google Scholar
• De Souza JA, Davis DW, Zhang Y, et al. A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res. 2012;18(8):2336–2343.
   PubMed Web of Science ®Google Scholar
• Weiss J, Hayes DN, Algazy K, et al. Combination lapatinib and capecitabine in advanced, incurable squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol. 2013;31(suppl):Abstract 6094.
   Google Scholar
• Harrington K, Berrier A, Robinson M, et al. Randomised phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: rationale for future randomised trials in human papilloma virus-negative disease. Eur J Cancer. 2013;49(7):1609–1618.
   PubMed Web of Science ®Google Scholar
• Ioannou N, Seddon AM, Dalgleish A, et al. Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells. BMC Cancer. 2013;13:41.
   PubMed Web of Science ®Google Scholar
• GILOTRIF^® (afatinib) tablets, for oral use [package insert]. Ridgefield (CT): Boehringer Ingelheim Pharmaceuticals; 2014.
   Google Scholar
• Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008;27(34):4702–4711.
   PubMed Web of Science ®Google Scholar
• Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther. 2012;343:342–350.
   PubMed Web of Science ®Google Scholar
• Seiwert TY, Fayette J, Cupissol D, et al. A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck. Ann Oncol. 2014;25(9):1813–1820.
   PubMed Web of Science ®Google Scholar
• Machiels JP, Licitra LF, Haddad RI, et al. Rationale and design of LUX-Head & Neck 1: a randomised, Phase III trial of afatinib versus methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma who progressed after platinum-based therapy. BMC Cancer. 2014;14:473.
   PubMed Web of Science ®Google Scholar
• Cohen EEW, Fayette LJ, Gauler TC, et al. Biomarker analysis in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients (pts) treated with second-line afatinib versus methotrexate (MTX): LUX-Head & Neck 1 (LUX-H&N1). J Clin Oncol. 2015;33(suppl):Abstract 6023.
   Google Scholar
• Engelman JA, Zejnullahu K, Gale CM, et al. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res. 2007;67(24):11924–11932.
   PubMed Web of Science ®Google Scholar
• Abdul Razak AR, Soulières D, Laurie SA, et al. A phase II trial of dacomitinib, an oral pan-human EGF receptor (HER) inhibitor, as first-line treatment in recurrent and/or metastatic squamous-cell carcinoma of the head and neck. Ann Oncol. 2013;24(3):761–769.
   PubMed Web of Science ®Google Scholar
• Brana I, She D, Chau NG, et al. Preoperative window-of-opportunity (WOO) study of dacomitinib (Dac) in patients (Pts) with resectable oral cavity squamous cell carcinoma (OCC): generation of a gene expression signature (DGS) as a predictor of Dac activity. J Clin Oncol. 2014;32(5s):Abstract 6041.
   Google Scholar
• Kamath AV, Lu D, Gupta P, et al. Preclinical pharmacokinetics of MEHD7945A, a novel EGFR/HER3 dual-action antibody, and prediction of its human pharmacokinetics and efficacious clinical dose. Cancer Chemother Pharmacol. 2012;69(4):1063–1069.
   PubMed Web of Science ®Google Scholar
• Huang S, Li C, Armstrong EA, et al. Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation. Cancer Res. 2013;73(2):824–833.
   PubMed Web of Science ®Google Scholar
• Francis DM, Huang S, Armstrong EA, et al. Pan-HER inhibitor augments radiation response in human lung and head and neck cancer models. Clin Cancer Res. 2016;22(3):633–643.
   PubMed Web of Science ®Google Scholar
• Pedersen MW, Jacobsen HJ, Koefoed K, et al. Sym004: a novel synergistic anti-epidermal growth factor receptor antibody mixture with superior anticancer efficacy. Cancer Res. 2010;70(2):588–597.
   PubMed Web of Science ®Google Scholar
• Skartved NJ, Jacobsen HJ, Pedersen MW, et al. Preclinical pharmacokinetics and safety of Sym004: a synergistic antibody mixture directed against epidermal growth factor receptor. Clin Cancer Res. 2011;17(18):5962–5972.
   PubMed Web of Science ®Google Scholar
• Huang S, Peet CR, Saker J, et al. Sym004, a novel anti-EGFR antibody mixture, augments radiation response in human lung and head and neck cancers. Mol Cancer Ther. 2013;12(12):2772–2781.
   PubMed Web of Science ®Google Scholar
• Machiels JP, Specenier P, Krauss J, et al. A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol. 2015;76(1):13–20.
   PubMed Web of Science ®Google Scholar
• Lai SY, Koppikar P, Thomas SM, et al. Intratumoral epidermal growth factor receptor antisense DNA therapy in head and neck cancer: first human application and potential antitumor mechanisms. J Clin Oncol. 2009;27(8):1235–1242.
   PubMed Web of Science ®Google Scholar
• Argiris A, Kotsakis AP, Hoang T, et al. Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2013;24(1):220–225.
   PubMed Web of Science ®Google Scholar
• Wen Y, Grandis JR. Emerging drugs for head and neck cancer. Expert Opin Emerg Drugs. 2015;20(2):313–329.
   PubMed Web of Science ®Google Scholar
• Sacco AG, Cohen EE. Current treatment options for recurrent or metastatic head and neck squamous cell carcinoma. J Clin Oncol. 2015;33(29):3305–3313.
   PubMed Web of Science ®Google Scholar
• Ferris RL. Immunology and immunotherapy of head and neck cancer. J Clin Oncol. 2015;33(29):3293–3304.
   PubMed Web of Science ®Google Scholar
• Langer CJ. Exploring biomarkers in head and neck cancer. Cancer. 2012;118(16):3882–3892.
   PubMed Web of Science ®Google Scholar