Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer

Bradley A. Schiff, Andrea B. McMurphy, Samar A. Jasser, Maher N. Younes, Dao Doan, Orhan G. Yigitbasi, Seungwon Kim, Ge Zhou, Mahitosh Mandal, Benjamin N. Bekele, F. Christopher Holsinger, Steven I. Sherman, Sai Ching Yeung, Adel K. El-Naggar, Jeffrey N. Myers

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)8594-8602
Number of pages9
JournalClinical Cancer Research
Volume10
Issue number24
DOIs
StatePublished - Dec 15 2004
Externally publishedYes

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Epidermal Growth Factor Receptor
Growth
Epidermal Growth Factor
Cell Proliferation
Apoptosis
Nude Mice
Anaplastic Thyroid Carcinoma
gefitinib
Paclitaxel
Tumor Cell Line
Thyroid Neoplasms
Neoplasms
Research Design
Therapeutics
In Vitro Techniques
Clinical Trials
Cell Line
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer. / Schiff, Bradley A.; McMurphy, Andrea B.; Jasser, Samar A.; Younes, Maher N.; Doan, Dao; Yigitbasi, Orhan G.; Kim, Seungwon; Zhou, Ge; Mandal, Mahitosh; Bekele, Benjamin N.; Holsinger, F. Christopher; Sherman, Steven I.; Yeung, Sai Ching; El-Naggar, Adel K.; Myers, Jeffrey N.

In: Clinical Cancer Research, Vol. 10, No. 24, 15.12.2004, p. 8594-8602.

Research output: Contribution to journalArticle

Schiff, BA, McMurphy, AB, Jasser, SA, Younes, MN, Doan, D, Yigitbasi, OG, Kim, S, Zhou, G, Mandal, M, Bekele, BN, Holsinger, FC, Sherman, SI, Yeung, SC, El-Naggar, AK & Myers, JN 2004, 'Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer', Clinical Cancer Research, vol. 10, no. 24, pp. 8594-8602. https://doi.org/10.1158/1078-0432.CCR-04-0690
Schiff, Bradley A. ; McMurphy, Andrea B. ; Jasser, Samar A. ; Younes, Maher N. ; Doan, Dao ; Yigitbasi, Orhan G. ; Kim, Seungwon ; Zhou, Ge ; Mandal, Mahitosh ; Bekele, Benjamin N. ; Holsinger, F. Christopher ; Sherman, Steven I. ; Yeung, Sai Ching ; El-Naggar, Adel K. ; Myers, Jeffrey N. / Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 24. pp. 8594-8602.
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abstract = "Purpose: 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. Experimental Design: 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.",
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T1 - Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer

AU - Schiff, Bradley A.

AU - McMurphy, Andrea B.

AU - Jasser, Samar A.

AU - Younes, Maher N.

AU - Doan, Dao

AU - Yigitbasi, Orhan G.

AU - Kim, Seungwon

AU - Zhou, Ge

AU - Mandal, Mahitosh

AU - Bekele, Benjamin N.

AU - Holsinger, F. Christopher

AU - Sherman, Steven I.

AU - Yeung, Sai Ching

AU - El-Naggar, Adel K.

AU - Myers, Jeffrey N.

PY - 2004/12/15

Y1 - 2004/12/15

N2 - Purpose: 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. Experimental Design: 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.

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