ZD1839 (‘Iressa’), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model

Williams, Kaye J.; Telfer, Brian A.; Stratford, Ian J.; Wedge, Stephen R.

doi:10.1038/sj.bjc.6600182

Cited by 161 publications

(50 citation statements)

References 16 publications

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“…Similar enhancement of activity has also been observed in studies combining EGFR-targeting agents, particularly the monoclonal antibody IMC C225 (cetuximab), with ionizing radiation (Huang et al, 1999;Saleh et al, 1999;Bianco et al, 2000;Bonner et al, 2000;Milas et al, 2000). Other investigators (Williams et al, 2002) and this laboratory (Magné et al, 2002a) recently showed supra-additive effects between irradiation and ZD1839, confirming the radiosensitisation conferred by an EGFRtargeting agent. We also reported a synergistic interaction between ZD1839 and the cisplatin -5FU combination (Magné et al, 2002a).…”

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confidence: 58%

Molecular mechanisms underlying the interaction between ZD1839 (‘Iressa’) and cisplatin/5-fluorouracil

et al. 2003

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ZD1839 ('Iressa'), an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is currently being investigated in clinical trials as a treatment for cancer. 'Iressa' is a trademark of the AstraZeneca group of companies. We have previously demonstrated a synergistic interaction between ZD1839 and cisplatin/5-fluorouracil (5FU) in CAL33, a human head and neck cancer cell line that markedly expresses EGFR. This study examined the effects of this drug combination on the cell cycle, cell cycle regulators, apoptosis-related factors, EGFR-related signalling and DNA repair in CAL33 cells. The cells were incubated with ZD1839 alone for 48 h, then cisplatin and 5FU were added. Exposure to the drug combination continued for a further 48 h. ZD1839 alone induced accumulation of cells in the G0/G1 phase of the cell cycle at 24 h accompanied by a concomitant increase in p21, p27 and Bax, a significant decrease in Bcl2 and a decrease in Akt phosphorylation. A decrease in DNA-PK was observed at 48 h. ZD1839 alone had no effect on caspase-3 activity, but addition of ZD1839 to cisplatin-5FU led to a significant increase in caspase-3 activity at 96 h. Thus, ZD1839 affects key cellular pathways controlling cell proliferation, apoptosis and DNA repair. These data provide a rationale to support clinical trials combining ZD1839 and cisplatin -5FU and other protocols that combine EGFR-targeting agents with chemotherapy or radiotherapy.

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confidence: 58%

Molecular mechanisms underlying the interaction between ZD1839 (‘Iressa’) and cisplatin/5-fluorouracil

et al. 2003

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“…6 Also, gefitinib has shown antitumoral activity against a range of human tumor xenografts. 7 To see if any other types of human cancers besides NSCLC carry the EGFR mutations, we analyzed 537 tissue samples from common human cancers, including 98 colon adenocarcinomas, 185 gastric adenocarcinomas, 93 breast ductal carcinomas, 73 hepatocellular carcinomas and 88 acute adulthood leukemias by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. Malignant cells and normal cells were selectively procured from hematoxylin and eosin-stained slides using a 30G1/2 hypodermic needle (Becton Dickinson, Franklin Lakes, NJ) affixed to a micromanipulator, as described previously.…”

Section: Dear Sirmentioning

confidence: 99%

“…Because gefitinib had an anti-cancer activity in wide types of cancer cell lines and the EGFR kinase domain mutation is known to mediate the gefitinib sensitivity, 6,7 we expected that human cancer tissues would widely carry EGFR mutations. However, our data showed that EGFR kinase domain is very rarely mutated in common human cancers besides NSCLC.…”

Section: Dear Sirmentioning

confidence: 99%

Absence of EGFR mutation in the kinase domain in common human cancers besides non‐small cell lung cancer

Lee

Soung

Kim

et al. 2004

Intl Journal of Cancer

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“…Recent studies have suggested that gefitinib induces cell cycle retardation and apoptosis, and inhibits the growth of several types of human cancer cells expressing EGFR both in vitro and in vivo (Ciardiello et al, 2000;Sirotnak et al, 2000;Ciardiello et al, 2001;Moasser et al, 2001;Moulder et al, 2001;Bianco et al, 2002;Ciardiello et al, 2002;Fujimura et al, 2002;Huang et al, 2002;Janne et al, 2002;Magne et al, 2002;Williams et al, 2002). In addition, human breast cancer cells overexpressing HER2 or acquiring resistance to the oestrogen receptor (ER) antagonist, fulvestrant (Faslodex,ICI 182,780), have been reported to be particularly sensitive to gefitinib (McClelland et al, 2001;Moulder et al, 2001).…”

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confidence: 99%

Additive antitumour effect of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant (Faslodex, ICI 182,780) in breast cancer cells

et al. 2004

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A high expression level of epidermal growth factor receptor (EGFR)/HER1 has been suggested to lead to a shorter survival time and resistance to endocrine therapy in patients with breast cancer. To test the hypothesis that inhibition of the EGFR signalling pathway affects the antitumour effect of endocrine therapy, an EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib, and an oestrogen receptor (ER) antagonist, fulvestrant, were administered to human breast cancer cells. A total of five human breast cancer cell lines were used. The effects of single or combined treatments with gefitinib and/or fulvestrant on cell growth, cell cycle progression and apoptosis were analysed. Changes in the expression levels of cyclin-dependent kinase inhibitors, p21 and p27, an antiapoptotic factor, Bcl-2, and a proapoptotic factor, Bax, were also investigated. All cell lines tested were sensitive to gefitinib (50% growth inhibitory concentration, 10 -28.5 mM). Breast cancer cell lines with a high expression level of HER1 or HER2 were more sensitive to gefitinib than the others. Gefitinib induced a significant G1 -S blockade in ER-positive KPL-3C cells. Gefitinib induced significant apoptosis in HER1-overexpressing MDA-MB-231 cells. Gefitinib additively increased the antitumour effect of fulvestrant in all three ER-positive cell lines in a medium supplemented with 17b-oestradiol. The combined treatment promoted cell cycle retardation in KPL-3C cells, which is associated with an upregulation of p21 by fulvestrant and gefitinib, respectively. Apoptosis was associated with downregulation of Bcl-2 by gefitinib in MDA-MB-231 cells. These results suggest an additive interaction between the EGFR-TKI gefitinib and the antioestrogen fulvestrant in ER-positive breast cancer cells.

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ZD1839 (‘Iressa’), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model

Cited by 161 publications

References 16 publications

Molecular mechanisms underlying the interaction between ZD1839 (‘Iressa’) and cisplatin/5-fluorouracil

Molecular mechanisms underlying the interaction between ZD1839 (‘Iressa’) and cisplatin/5-fluorouracil

Absence of EGFR mutation in the kinase domain in common human cancers besides non‐small cell lung cancer

Additive antitumour effect of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant (Faslodex, ICI 182,780) in breast cancer cells

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