Combined Modality Therapy of A431 Human Epidermoid Cancer Using Anti-EGFr Antibody C225 and Radiation

Saleh, Mansoor N.; Raisch, Kevin P.; Stackhouse, Murray; Grizzle, William E.; Bonner, James A.; Mayo, Matthew S.; Kim, Hyung‐Gyoon; Meredith, Ruby F.; Wheeler, Richard; Buchsbaum, Donald J.

doi:10.1089/cbr.1999.14.451

Cited by 144 publications

(65 citation statements)

References 2 publications

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“…EGFR is stimulated by a number of autocrine growth factors, including EGF and TGFa. Recently, it has been shown that ionising radiation stimulates EGFR activation and cellular proliferation (Schmidt-Ullrich et al, 1997; Dent et al, 1999;Reardon et al, 1999;Todd et al, 1999) and that anti-EGFR antibody approaches can improve tumour radiation response (Saleh et al, 1999;Bianco et al, 2000;Milas et al, 2000). In the present study, we evaluated the potential influence of ZD1839 on the radiation response of the human colorectal carcinoma cell line LoVo which has moderate levels of EGFR expression (33 000 receptors per cell), and is therefore likely to be representative of most epithelial tumour cell lines (Caraglia et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2002

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The effect of ZD1839 (‘Iressa’), a specific inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor, on the radiation response of human tumour cells (LoVo colorectal carcinoma) was evaluated in vitro and in vivo . ZD1839 (0.5 μ M , incubated days 1–5) significantly increased the anti-proliferative effect of fractionated radiation treatment (2 Gy day −1 , days 1–3) on LoVo cells grown in vitro ( P =0.002). ZD1839 combined with either single or fractionated radiotherapy in mice bearing LoVo tumour xenografts, also produced a highly significant increase in tumour growth inhibition ( P ⩽0.001) when compared to treatment with either modality alone. The radio-potentiating effect of ZD1839 was more apparent when radiation was administered in a fractionated protocol. This phenomenon may be attributed to an anti proliferative effect of ZD1839 on tumour cell re-population between radiotherapy fractions. These data suggest radiotherapy with adjuvant ZD1839 could enhance treatment response. Clinical investigation of ZD1839 in combination with radiotherapy is therefore warranted. British Journal of Cancer (2002) 86 , 1157–1161. DOI: 10.1038/sj/bjc/6600182 www.bjcancer.com © 2002 Cancer Research UK

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Section: Discussionmentioning

confidence: 99%

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

et al. 2002

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“…There are numerous experimental data both in vitro and in vivo showing that EGFR targeting is able to augment the antitumour activity of several anticancer agents including doxorubicin, cisplatin, 5-fluorouracil (5FU), gemcitabine, paclitaxel and topotecan Fan et al, 1993;Ciardiello et al, 1999;Bruns et al, 2000;Inoue et al, 2000;Overholser et al, 2000). 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.…”

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confidence: 81%

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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“…These preclinical indications suggest a role for cetuximab in irinotecan-refractory CRC patients (Prewett et al, 2002). Several preclinical studies have also shown an enhancement of tumor response to radiotherapy by combined treatment with cetuximab in human epidermoid, head and neck, and colon cancer xenografts (Huang et al, 1999;Saleh et al, 1999;Bianco et al, 2000;Huang and Harari, 2000;Milas et al, 2000). Among the potential mechanisms that contribute to the increased radiation sensitivity by treatment with cetuximab, it has been suggested an accumulation of cancer cells in the more radiosensitive cell-cycle phases (G 1 , G 2 -M), a blockade of radiation-induced DNA repair mechanisms, a reduction of VEGF production by cancer cells with inhibition of tumor angiogenesis (Huang and Harari, 2000).…”

Section: Molecular Properties and Clinical Pharmacologymentioning

confidence: 99%

Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer

et al. 2007

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The recent successful development of monoclonal antibodies that target key components of biological pathways has expanded the armamentarium of treatment options for patients with colorectal cancer (CRC). In particular, the epidermal growth factor receptor (EGFR), a tyrosine kinase growth factor receptor involved in CRC development and progression, is exploited by the newest monoclonal antibody that is available for use in CRC patients. Cetuximab, the first chimeric monoclonal antibody, which has been generated against the EGFR, is currently registered in USA, Europe and worldwide, in combination with irinotecan in the treatment of metastatic CRC patients who have progressed on irinotecan containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Furthermore, a series of phase III clinical trials are currently evaluating the combination of cetuximab with standard chemotherapy regimens in the first-line treatment chemotherapy-naı¨ve patients with metastatic CRC.

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Combined Modality Therapy of A431 Human Epidermoid Cancer Using Anti-EGFr Antibody C225 and Radiation

Cited by 144 publications

References 2 publications

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

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

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

Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer

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