{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:18:20Z","timestamp":1789967900358,"version":"4.0.1"},"reference-count":81,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T00:00:00Z","timestamp":1539129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Program of the Department of Investigation of the Universidad Ju\u00e1rez del Estado de Durango and Research Institute in Dentistry of the Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara.","award":["UJED-CA-109"],"award-info":[{"award-number":["UJED-CA-109"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>This manuscript provides an update to the literature on molecules with roles in tumor resistance therapy in head and neck squamous cell carcinoma (HNSCC). Although significant improvements have been made in the treatment for head and neck squamous cell carcinoma, physicians face yet another challenge\u2014that of preserving oral functions, which involves the use of multidisciplinary therapies, such as multiple chemotherapies (CT) and radiotherapy (RT). Designing personalized therapeutic options requires the study of genes involved in drug resistance. This review provides an overview of the molecules that have been linked to resistance to chemotherapy in HNSCC, including the family of ATP-binding cassette transporters (ABCs), nucleotide excision repair\/base excision repair (NER\/BER) enzymatic complexes (which act on nonspecific DNA lesions generated by gamma and ultraviolet radiation by cross-linking and forming intra\/interchain chemical adducts), cisplatin (a chemotherapeutic agent that causes DNA damage and induces apoptosis, which is a paradox because its effectiveness is based on the integrity of the genes involved in apoptotic signaling pathways), and cetuximab, including a discussion of the genes involved in the cell cycle and the proliferation of possible markers that confer resistance to cetuximab.<\/jats:p>","DOI":"10.3390\/cancers10100376","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T11:53:13Z","timestamp":1539172393000},"page":"376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Molecular Markers of Anticancer Drug Resistance in Head and Neck Squamous Cell Carcinoma: A Literature Review"],"prefix":"10.3390","volume":"10","author":[{"given":"Sandra","family":"L\u00f3pez-Verd\u00edn","sequence":"first","affiliation":[{"name":"Research Institute of Dentistry, Health Science Center, Universidad de Guadalajara, Guadalajara 4430, JAL, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Lavalle-Carrasco","sequence":"additional","affiliation":[{"name":"Department of Research, School of Dentistry, Universidad Ju\u00e1rez del Estado de Durango, Durango 34000, DGO, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n G.","family":"Carre\u00f3n-Burciaga","sequence":"additional","affiliation":[{"name":"Department of Research, School of Dentistry, Universidad Ju\u00e1rez del Estado de Durango, Durango 34000, DGO, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0402-3985","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Seraf\u00edn-Higuera","sequence":"additional","affiliation":[{"name":"Molecular Biology Department, School of Dentistry, Universidad Aut\u00f3noma de Baja California, Mexicali 21040, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Molina-Frechero","sequence":"additional","affiliation":[{"name":"Department of Health Care, Xochimilco Unit, Universidad Aut\u00f3noma Metropolitana (UAM) Xochimilco, Mexico City  04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4457-704X","authenticated-orcid":false,"given":"Rogelio","family":"Gonz\u00e1lez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Research, School of Dentistry, Universidad Ju\u00e1rez del Estado de Durango, Durango 34000, DGO, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9755-4779","authenticated-orcid":false,"given":"Ronell","family":"Bologna-Molina","sequence":"additional","affiliation":[{"name":"Department of Research, School of Dentistry, Universidad Ju\u00e1rez del Estado de Durango, Durango 34000, DGO, Mexico"},{"name":"Molecular Pathology Area, School of Dentistry, Universidad de la Rep\u00fablica, Montevideo 11600, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/carcin\/bgp220","article-title":"Epigenetics in cancer","volume":"31","author":"Sharma","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1056\/NEJMra072067","article-title":"Epigenetics in cancer","volume":"13","author":"Esteller","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jormas.2017.05.004","article-title":"The promising impact of molecular profiling on treatment strategies in oral cancers","volume":"118","author":"Foy","year":"2017","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Irimie, A.I., Ciocan, C., Gulei, D., Mehterov, N., Atanasov, A.G., Dudea, D., and Berindan-Neagoe, I. (2018). Current Insights into oral cancer epigenetics. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030670"},{"key":"ref_5","first-page":"189","article-title":"Lack of survival advantage in patients with advanced, resectable squamous cell carcinoma of the oral cavity receiving induction chemotherapy with cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU)","volume":"50","author":"Umeda","year":"2004","journal-title":"Kobe J. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/sj.bjc.6601471","article-title":"Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)","volume":"90","author":"Katori","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/jop.12310","article-title":"Epidermal growth factor is a potential biomarker for poor cetuximab response in tongue cancer cells","volume":"45","author":"Ansell","year":"2016","journal-title":"J. Oral Pathol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/1097-0142(19880715)62:2<251::AID-CNCR2820620205>3.0.CO;2-J","article-title":"Neoadjuvant chemotherapy in previously untreated patients with advanced head and neck squamous cell cancer","volume":"62","author":"Cognelti","year":"1988","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/1097-0142(19830415)51:8<1353::AID-CNCR2820510805>3.0.CO;2-I","article-title":"Adjuvant chemotherapy with cisdiamminedichloroplatinum and 120-hour infusion 5-fluorouracil in stage III and IV squamous cell carcinoma of the head and neck","volume":"51","author":"Decker","year":"1983","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1200\/JCO.1987.5.1.10","article-title":"An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous cell carcinoma of the head and neck","volume":"5","author":"Ervin","year":"1987","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/hed.10204","article-title":"Differentially expressed genes associated with ClS-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and cDNA microarray","volume":"25","author":"Higuchi","year":"2003","journal-title":"Head Neck"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s13577-010-0004-x","article-title":"Heterogeneity of anticancer drug sensitivity in squamous cell carcinoma of the tongue","volume":"24","author":"Suzuki","year":"2011","journal-title":"Hum. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nrg2841","article-title":"Advances in understanding cancer genomes through second-generation sequencing","volume":"11","author":"Meyerson","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6919","DOI":"10.7314\/APJCP.2015.16.16.6919","article-title":"Outcome of Palliative and Radical Radiotherapy in Patients with Oral Squamous Cell Carcinoma\u2014A Retrospective Study","volume":"16","author":"Rai","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/bjc.1990.146","article-title":"Has chemotherapy proved itself in head and neck cancer?","volume":"6","author":"Tobias","year":"1990","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1007\/s11538-017-0334-x","article-title":"Modeling the Transfer of Drug Resistance in Solid Tumors","volume":"79","author":"Becker","year":"2017","journal-title":"Bull. Math. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Weinberg, R. (2013). The Rational Treatment of Cancer in the Biology of Cancer, Garland Science. [2nd ed.].","DOI":"10.1201\/9780429258794"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2174\/187152013804487380","article-title":"New insight into p-glycoprotein as a drug target","volume":"13","author":"Breier","year":"2013","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_19","first-page":"4980","article-title":"Prevalence of multidrug resistance related to activation of the mdr1 gene in human sarcoma mutants derived by single-step doxorubicin selection","volume":"54","author":"Chen","year":"1994","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/(SICI)1097-0142(19980901)83:5<851::AID-CNCR8>3.0.CO;2-L","article-title":"Expression of p-glycoprotein, a multidrug-resistance gene product, is induced by radiotherapy in patients with oral squamous cell carcinoma","volume":"83","author":"Ng","year":"1998","journal-title":"Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1288\/00005537-199512000-00006","article-title":"P-glycoprotein expression in the squamous cell carcinoma of the tongue base","volume":"105","author":"Rabkin","year":"1995","journal-title":"Laryngoscope"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/(SICI)1097-0215(19970220)74:1<128::AID-IJC21>3.0.CO;2-A","article-title":"Differential expression of multidrug resistance gene product, P-glycoprotein, in normal, dysplastic and malignant oral mucosa in India","volume":"74","author":"Jain","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1093\/jnci\/85.8.632","article-title":"Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs","volume":"85","author":"Chaudhary","year":"1993","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_24","first-page":"459","article-title":"Sequential coexpression of the multidrug resistance genes MRP and mdr1 and their products in VP-16 (etoposide)-selected H69 small cell lung cancer cells","volume":"55","author":"Brock","year":"1995","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1038\/bjc.1996.655","article-title":"P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo","volume":"74","author":"Abe","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/bjc.1995.180","article-title":"Rapid up-regulation of mdr1 expression by anthracyclines in a classical multidrug-resistant cell line","volume":"71","author":"Hu","year":"1995","journal-title":"Br. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1111\/j.1349-7006.1988.tb01550.x","article-title":"Vincristine-resistant human cancer KB cell line and increased expression of multidrug-resistance gene","volume":"79","author":"Kohno","year":"1988","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1134\/S0006297918070015","article-title":"Recent Advances in the Studies of Molecular Mechanisms Regulating Multidrug Resistance in Cancer Cells","volume":"83","author":"Stavrovskaya","year":"2018","journal-title":"Biochemistry (Mosc)"},{"key":"ref_29","first-page":"133","article-title":"Expression of multi-drug resistance genes (mdr1, mrp1, bcrp) in primary oral squamous cell carcinoma","volume":"18","author":"Friedrich","year":"2004","journal-title":"In Vivo"},{"key":"ref_30","first-page":"1281","article-title":"Establishment and characterization of a cisplatin-resistant oral squamous cell carcinoma cell line, H-1R","volume":"14","author":"Nakamura","year":"2005","journal-title":"Oncol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29538","DOI":"10.18632\/oncotarget.25268","article-title":"Polymorphism in DNA mismatch repair pathway genes predict toxicity and response to cisplatin chemoradiation in head and neck squamous cell carcinoma patients","volume":"9","author":"Nogueira","year":"2018","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1158\/1078-0432.CCR-06-1911","article-title":"Nucleotide Excision Repair Pathway Genes and Oral Premalignant Lesions","volume":"13","author":"Wang","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Visnes, T., Grube, M., Hanna, B.M.F., Benitez-Buelga, C., C\u00e1zares-K\u00f6rner, A., and Helleday, T. (2018). Targeting BER enzymes in cancer therapy. DNA Repair, in press.","DOI":"10.1016\/j.dnarep.2018.08.015"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.1200\/JCO.2006.05.8768","article-title":"DNA-Repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy","volume":"24","author":"Hitt","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_35","first-page":"47","article-title":"ERCC1 and XRCC1 as biomarkers for lung and head and neck cancer","volume":"4","author":"Vaezi","year":"2011","journal-title":"Pharmgenomics. Pers. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"87","DOI":"10.7314\/APJCP.2016.17.S3.87","article-title":"ERCC1 Expression can predict response to platinum-based induction chemotherapy in head and neck cancer cases","volume":"17","author":"Ameri","year":"2016","journal-title":"Asian Pac. J. Can. Prev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.oraloncology.2011.07.028","article-title":"Antitumor activity of cetuximab associated with the taxotere-cisplatin-fluorouracil (TPF) combination on an orthotopic head and neck cancer model","volume":"47","author":"Bozec","year":"2011","journal-title":"Oral Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.3892\/ol.2015.3458","article-title":"Combined paclitaxel, cisplatin and fluorouracil therapy enhances ionizing radiation effects, inhibits migration and induces G0\/G1 cell cycle arrest and apoptosis in oral carcinoma cell lines","volume":"10","author":"Elias","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1200\/JCO.2000.18.7.1465","article-title":"p53 alterations predict tumor response to neoadjuvant chemotherapy in head and neck squamous cell carcinoma: a prospective series","volume":"18","author":"Cabelguenne","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.bjoms.2013.05.150","article-title":"Evaluation of p53 as a prognostic factor for oral cancer surgery","volume":"51","author":"Cutilli","year":"2013","journal-title":"Br. J. Oral Maxillofac Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1054\/drup.2001.0210","article-title":"The role of Fas and FasL as mediators of anticancer chemotherapy","volume":"4","author":"Poulaki","year":"2001","journal-title":"Drug Resist. Updat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"281","DOI":"10.7314\/APJCP.2013.14.1.281","article-title":"Effects of FasL expression in oral squamous cell cancer","volume":"14","author":"Fang","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1158\/1535-7163.MCT-16-0314","article-title":"A Fas Ligand (FasL)-Fused Humanized Antibody Against Tumor-Associated Glycoprotein 72 Selectively Exhibits the Cytotoxic Effect Against Oral Cancer Cells with a Low FasL\/Fas Ratio","volume":"16","author":"Chien","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1158\/1078-0432.CCR-1116-03","article-title":"Matrix Metalloproteinase 3 polymorphism: A predictive factor of response to noadjuvant chemotherapy in head and neck squamous cell carcinoma","volume":"10","author":"Blons","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jim.2018.02.004","article-title":"CRISPR\/Cas9 generated human CD46, CD55 and CD59 knockout cell lines as a tool for complement research","volume":"456","author":"Thielen","year":"2018","journal-title":"J. Immunol. Methods."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1182\/blood.V98.9.2771","article-title":"Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase-independent mechanism involving the generation of reactive oxygen species","volume":"98","author":"Bellosillo","year":"2001","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.4110\/in.2018.18.e11","article-title":"Beyond the Role of CD55 as a Complement Component","volume":"18","author":"Dho","year":"2018","journal-title":"Immune Netw."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ma, W., Concha-Benavente, F., Santegoets, S.J.A.M., Welters, M.J.P., Ehsan, I., Ferris, R.L., and van der Burg, S.H. (2018). EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine secretion in head and neck cancer. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203402"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"780","DOI":"10.3892\/or.2014.3258","article-title":"Resistance of oral squamous cell carcinoma cells to cetuximab is associated with EGFR insensitivity and enhanced stem cell-like potency","volume":"32","author":"Ohnishi","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1056\/NEJMoa053422","article-title":"Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck","volume":"354","author":"Bonner","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ccr.2005.03.003","article-title":"Structural basis for inhibition of the epidermal growth factor receptor by cetuximab","volume":"7","author":"Li","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_52","first-page":"871","article-title":"Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck","volume":"3","author":"Merlano","year":"2007","journal-title":"Ther. Clin. Risk. Manag."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1677\/erc.0.0080083","article-title":"EGF mutant receptor vIII as a molecular target in cancer therapy","volume":"8","author":"Kuan","year":"2001","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_54","first-page":"1547","article-title":"Effective targeting of the epidermal growth factor receptor (EGFR) for treating oral cancer: A promising approach","volume":"34","author":"Ribeiro","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/jcp.21635","article-title":"The epidermal growth factor receptor ligands at a glance","volume":"218","author":"Schneider","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/mt.2009.226","article-title":"Amphiregulin promotes BAX inhibition and resistance to gefitinib in non-small-cell lung cancers","volume":"18","author":"Busser","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5197","DOI":"10.1158\/1078-0432.CCR-10-3338","article-title":"Expression of amphiregulin and EGFRvIII outcome of patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment","volume":"17","author":"Tinhofer","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hatakeyama, H., Cheng, H., Wirth, P., Counsell, A., Marcrom, S.R., Wood, C.B., Pohlmann, P.R., Gilbert, J., Murphy, B., and Yarbrough, W.G. (2010). 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.","DOI":"10.1371\/journal.pone.0012702"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1634\/theoncologist.2013-0013","article-title":"Anti-epidermal growth factor receptor therapy in head and neck squamous cell carcinoma: Focus on potential molecular mechanisms of drug resistance","volume":"18","author":"Boeckx","year":"2013","journal-title":"Oncologist"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"102371","DOI":"10.18632\/oncotarget.21987","article-title":"The role of anti-EGFR agents in patients with locoregionally advanced head and neck cancer: A meta-analysis of randomized trials","volume":"8","author":"Kim","year":"2017","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1111\/j.1600-0854.2009.00943.x","article-title":"Differential effects of EGFR ligands on endocytic sorting of the receptor","volume":"10","author":"Roepstorff","year":"2009","journal-title":"Traffic"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1038\/sj.onc.1208752","article-title":"Aurora kinases: shining lights on the therapeutic horizon?","volume":"24","author":"Andrews","year":"2005","journal-title":"Oncogene"},{"key":"ref_63","first-page":"1631","article-title":"Aurora-A\/STK15\/BTAK enhances chromosomal instability in bladder cancer cells","volume":"25","author":"Fraizer","year":"2004","journal-title":"Int. J. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1186\/s12935-014-0091-y","article-title":"Association between genetic polymorphism in AURKA (rs2273535 and rs1047972) and breast cancer risk: a meta-analysis involving 37,221 subjects","volume":"14","author":"Dai","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chou, C.H., Chou, Y.E., Chuang, C.Y., Yang, S.F., and Lin, C.W. (2017). Combined effect of genetic polymorphisms of AURKA and environmental factors on oral cancer development in Taiwan. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171583"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"599","DOI":"10.18632\/oncotarget.311","article-title":"Aurora kinase inhibition overcomes cetuximab resistance in squamous cell cancer of the head and neck","volume":"2","author":"Hoellein","year":"2011","journal-title":"Oncotarget"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.18632\/oncotarget.2117","article-title":"The response of head and neck squamous cell carcinoma to cetuximab treatment depend on Aurora kinase A polymorphism","volume":"5","author":"Pickhard","year":"2014","journal-title":"Oncotarget."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"693","DOI":"10.3892\/ijo.2013.2225","article-title":"Snail-induced epithelial-mesenchymal transition promotes cancer stem cell-like phenotype in head and neck cancer cells","volume":"44","author":"Masui","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13488","DOI":"10.18632\/oncotarget.24416","article-title":"Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma","volume":"9","author":"Gammon","year":"2018","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"La Fleur, L., Johansson, A.C., and Roberg, K. (2012). A CD44high\/EGFRlow subpopulation within head and neck cancer cell lines shows an epithelial-mesenchymal transition phenotype and resistance to treatment. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044071"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.yexcr.2012.03.023","article-title":"Tumor cell and carcinoma-associated fibroblast interaction regulates matrix metalloproteinases and their inhibitors in oral squamous cell carcinoma","volume":"318","author":"Kovalszky","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5863","DOI":"10.4238\/2013.November.22.14","article-title":"Tumor-associated fibroblast-conditioned medium promotes tumor cell proliferation and angiogenesis","volume":"12","author":"Xu","year":"2013","journal-title":"Genet Mol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/CCO.0b013e32835b6371","article-title":"TGF-\u03b2 signaling and epithelial-mesenchymal transition in cancer progression","volume":"25","author":"Katsuno","year":"2013","journal-title":"Curr. Opin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.ijrobp.2009.08.079","article-title":"Phase I\/II study of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck","volume":"78","author":"Herchenhorn","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"43964","DOI":"10.18632\/oncotarget.6268","article-title":"Invasive oral cancer stem cells display resistance to ionising radiation","volume":"6","author":"Gemenetzidis","year":"2015","journal-title":"Oncotarget"},{"key":"ref_76","first-page":"2057","article-title":"Cytochrome P450: Polymorphisms and roles in Cancer, Diabetes and Atherosclerosis","volume":"19","author":"Elfaki","year":"2018","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/978-1-62703-321-3_21","article-title":"Update on allele nomenclature for human cytochromes P450 and the human cytochrome P450 allele (CYP-allele) nomenclature database","volume":"987","author":"Sim","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_78","first-page":"8","article-title":"Association of polymorphism in cytochrome P450 2C9 with susceptibility to head and neck cancer and treatment outcome","volume":"3","author":"Yadav","year":"2014","journal-title":"Appl. Transl. Genom."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.mayocp.2015.12.017","article-title":"Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment","volume":"91","author":"Marur","year":"2016","journal-title":"Mayo Clin. Proc."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Santarelli, A., Mascitti, M., Lo-Russo, L., Sartini, D., Troiano, G., Emanuelli, M., and Lo-Muzio, L. (2018). Survivin-Based Treatment Strategies for Squamous Cell Carcinoma. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040971"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.1038\/s41388-017-0110-2","article-title":"Piperlongumine and p53-reactivator APR-246 selectively induce cell death in HNSCC by targeting GSTP1","volume":"37","author":"Hang","year":"2018","journal-title":"Oncogene"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/10\/376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:24:40Z","timestamp":1760196280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/10\/376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,10]]},"references-count":81,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["cancers10100376"],"URL":"https:\/\/doi.org\/10.3390\/cancers10100376","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,10]]}}}