Enhancement of radiosensitivity in head and neck cancer cells by ZD1839 ('IRESSA'), a selective epidermal growth factor receptor tyrosine kinase inhibitor.

Satoru Shintani, Akihisa Kiyota, Mariko Mihara, Tomoki Sumida, Hiroaki Kayahara, Koh ichi Nakashiro, Hiroyuki Hamakawa

Research output: Contribution to journalArticle

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Abstract

Overexpression of epidermal growth factor receptor (EGFR) is frequently observed in many solid tumor types, including head and neck squamous cell carcinomas (HNSCC). Recent laboratory experiments have demonstrated that high EGFR levels correlate with increased tumor resistance to radiation. This study investigated the relationship between EGFR expression levels and radiosensitivity in 5 HNSCC cell lines (HSC2, HSC3, HSC4, SCC25, and Ca9-22) and whether treatment with ZD1839 ('Iressa'), a selective EGFR-tyrosine kinase inhibitor (TKI), would improve tumor cell response to radiotherapy. ZD1839 suppressed the growth of HNSCC cell lines in a dose- and time-dependent manner. Radiosensitivity of these HNSCC cell lines, assessed by a clonogenic survival assay, differed greatly and the expression of EGFR varied. EGFR expression levels (EGFR numbers/cell) correlated with increased tumor resistance to radiation (f[x]= 4.54 X, R2 = 0.715; f[x]: EGFR numbers/cell, X: radiosensitivity; D10). Following exposure of the HNSCC cells to 1.0 microM ZD1839 and radiation (0-10 Gy), greater than additive growth inhibitory effects were observed. These results suggest that ZD1839 could enhance tumor radiosensitivity and inhibit tumor growth after radiation, indicating that this combination could have clinical potential in the treatment of patients with head and neck cancer.

Original languageEnglish
JournalAmerican journal of clinical oncology
Volume26
Issue number5
Publication statusPublished - Jan 1 2003
Externally publishedYes

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Radiation Tolerance
Head and Neck Neoplasms
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Radiation
Neoplasms
Cell Line
Growth
Cell Count
gefitinib
Radiotherapy
Carcinoma, squamous cell of head and neck
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Enhancement of radiosensitivity in head and neck cancer cells by ZD1839 ('IRESSA'), a selective epidermal growth factor receptor tyrosine kinase inhibitor. / Shintani, Satoru; Kiyota, Akihisa; Mihara, Mariko; Sumida, Tomoki; Kayahara, Hiroaki; Nakashiro, Koh ichi; Hamakawa, Hiroyuki.

In: American journal of clinical oncology, Vol. 26, No. 5, 01.01.2003.

Research output: Contribution to journalArticle

Shintani, Satoru ; Kiyota, Akihisa ; Mihara, Mariko ; Sumida, Tomoki ; Kayahara, Hiroaki ; Nakashiro, Koh ichi ; Hamakawa, Hiroyuki. / Enhancement of radiosensitivity in head and neck cancer cells by ZD1839 ('IRESSA'), a selective epidermal growth factor receptor tyrosine kinase inhibitor. In: American journal of clinical oncology. 2003 ; Vol. 26, No. 5.
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