title: Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer.
abstract: OBJECTIVE
  No effective treatment options currently are available to patients with anaplastic thyroid cancer (ATC), resulting in high mortality rates. Epidermal growth factor (EGF) has been shown to play a role in the pathogenesis of many types of cancer, and its receptor (EGFR) provides an attractive target for molecular therapy.
  
  
  METHODS
  The expression of EGFR was determined in ATC in vitro and in vivo and in human tissue arrays of ATC. We assessed the potential of the EGFR inhibitor gefitinib ("Iressa," ZD1839) to inhibit EGFR activation in vitro and in vivo, inhibit ATC cellular proliferation, induce apoptosis, and reduce the growth of ATC cells in vivo when administered alone and in combination with paclitaxel.
  
  
  RESULTS
  EGFR was overexpressed in ATC cell lines in vitro and in vivo and in human ATC specimens. Activation of EGFR by EGF was blocked by the addition of gefitinib. In vitro studies showed that gefitinib greatly inhibited cellular proliferation and induced apoptosis in ATC cell lines and slowed tumor growth in a nude mouse model of thyroid carcinoma cells injected subcutaneously.
  
  
  CONCLUSIONS
  ATC cells consistently overexpress EGFR, rendering this receptor a potential target for molecular therapy. Gefitinib effectively blocks activation of EGFR by EGF, inhibits ATC cellular proliferation, and induces apoptosis in vitro. Our in vivo results show that gefitinib has significant antitumor activity against ATC in a subcutaneous nude mouse tumor model and therefore is a potential candidate for human clinical trials.
authors.affiliation: Department of Head and Neck Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Schiff
authors.forename: Andrea B
authors.initials: AB
authors.lastname: McMurphy
authors.forename: Samar A
authors.initials: SA
authors.lastname: Jasser
authors.forename: Maher N
authors.initials: MN
authors.lastname: Younes
authors.forename: Dao
authors.initials: D
authors.lastname: Doan
authors.forename: Orhan G
authors.initials: OG
authors.lastname: Yigitbasi
authors.forename: Seungwon
authors.initials: S
authors.lastname: Kim
authors.forename: Ge
authors.initials: G
authors.lastname: Zhou
authors.forename: Mahitosh
authors.initials: M
authors.lastname: Mandal
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Bekele
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Holsinger
authors.forename: Steven I
authors.initials: SI
authors.lastname: Sherman
authors.forename: Sai-Ching
authors.initials: SC
authors.lastname: Yeung
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000008:administration & dosage; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D016211:Transforming Growth Factor alpha / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017239:Paclitaxel; D000077156:Gefitinib