title: Overcoming cetuximab resistance in HNSCC: the role of AURKB and DUSP proteins.
abstract: Unraveling the underlying mechanisms of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC) is of major importance as many tumors remain non-responsive or become resistant. Our microarray results suggest that "resistant" cells still exhibit RAS-MAPK pathway signaling contributing to drug resistance, as witnessed by low expression of DUSP5 and DUSP6, negative regulators of ERK1/2, and increased expression of AURKB, a key regulator of mitosis. Therefore, interrupting the RAS-MAPK pathway by an ERK1/2 inhibitor (apigenin) or an AURKB inhibitor (barasertib) might be a new strategy for overcoming cetuximab resistance in HNSCC.
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium. Electronic address: carolien.boeckx@uatnwerpen.be.
authors.forename: Carolien
authors.initials: C
authors.lastname: Boeckx
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium; Center for Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium; Antwerp University Hospital, Wilrijkstraat 10, Antwerpen, Belgium.
authors.forename: Ken
authors.initials: K
authors.lastname: Op de Beeck
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Wouters
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Deschoolmeester
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium.
authors.forename: Ridha
authors.initials: R
authors.lastname: Limame
authors.affiliation: Department of Pathology, Antwerp University Hospital, Wilrijkstraat 10, Antwerpen, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Zwaenepoel
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium; Department of Medical Oncology, Antwerp University Hospital, Wilrijkstraat 10, Antwerpen, Belgium.
authors.forename: Pol
authors.initials: P
authors.lastname: Specenier
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium; Department of Pathology, Antwerp University Hospital, Wilrijkstraat 10, Antwerpen, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium; Department of Medical Oncology, Antwerp University Hospital, Wilrijkstraat 10, Antwerpen, Belgium.
authors.forename: Jan B
authors.initials: JB
authors.lastname: Vermorken
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium; Department of Medical Oncology, Antwerp University Hospital, Wilrijkstraat 10, Antwerpen, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Center for Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium; Antwerp University Hospital, Wilrijkstraat 10, Antwerpen, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Baay
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Universiteitsplein1, Wilrijk, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Lardon
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D064107:Aurora Kinase B / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010755:Organophosphates / Q000008:administration & dosage / Q000494:pharmacology; D000077544:Panitumumab; D010766:Phosphorylation; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D010755:Organophosphates; D011799:Quinazolines; D000077544:Panitumumab; C576921:AURKB protein, human; D064107:Aurora Kinase B; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054637:Dual-Specificity Phosphatases; D000068818:Cetuximab
keywords: Anti-EGFR therapy; Aurora kinase B; Cetuximab resistance; Dual-specificity phosphatase 5 and 6; Head and neck squamous cell carcinoma; NanoPro 1000