Cetuximab: An epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer

Wong, Siu-Fun

doi:10.1016/j.clinthera.2005.06.003

Cited by 217 publications

(134 citation statements)

References 21 publications

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“…This has resulted in the development of molecular therapies targeting EGFR and the subsequent approval of anti-EGFR monoclonal antibodies, such as cetuximab and panitumumab, for the treatment of patients with various types of cancer including metastatic CRC (11,14). However, despite extensive studies, there are currently no clear markers for predicting the response to therapy with the EGFR inhibitors (9).…”

Section: Discussionmentioning

confidence: 99%

“…These observations have led to the strategic development and approval of several erbB receptor targeting drugs, including the anti-EGFR monoclonal antibodies (mAbs), cetuximab and panitumumab, the anti-HER-2 mAb, Herceptin, the small molecule EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, as well as lapatinib, which is a dual reversible EGFR and HER-2 TKI, for the treatment of cancer patients (11)(12)(13)(14)(15). Of the EGFR inhibitors, cetuximab and panitumumab have been approved for the treatment of patients with metastatic CRC.…”

Section: Introductionmentioning

confidence: 99%

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Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

Modjtahedi¹

2011

Int J Oncol

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Abstract. Despite the approval of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs), cetuximab and panitumumab, for the treatment of colorectal cancer patients, there is currently no reliable predictive marker for response to therapy. In addition, the duration of response is often limited. Therefore, this study aimed to investigate the effect of afatinib, an irreversible erbB family blocker, as a single agent or in combination with cytotoxic drugs (5-fluorouracil, irinotecan and oxaliplatin) or mAb ICR62 on the proliferation of a panel of human colorectal tumour cell lines and the association between the expression levels of the EGFR family members and response to treatment. Of the cells examined, EGFR-overexpressing DiFi cells were the most sensitive to treatment with both afatinib (IC 50 =45 nM) and ICR62 (IC 50 =4.33 nM). Afatinib also inhibited the growth of other tumour cell lines with IC 50 values which ranged from 0.33 µM (CCL-221) to 1.62 µM (HCT-116). A significant association was found between the co-expression of EGFR, human epidermal growth factor receptor (HER)-2 and HER-3 and response to treatment with afatinib (R=0.915, P=0.021). Treatment with afatinib and cytotoxic drugs was accompanied by an increase in the proportion of these cells in the sub-G0/G1 and in the S and G2/M phase of the cell cycle, respectively. We conclude that afatinib as monotherapy or in combination with other drugs shows activity in colorectal tumour cells and that determination of the co-expression of HER family members should be conducted in clinical trials using drugs targeting erbB signaling. This approach could lead to the identification of a specific subpopulation of cancer patients more likely to benefit from erbB-directed therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

Modjtahedi¹

2011

Int J Oncol

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“…Cetuximab is an EGFR antibody approved for clinical use for metastatic colorectal cancer both as monotherapy and in combination with chemotherapy or radiation (16,17). Erlotinib and sunitinib are both tyrosine kinase inhibitors but erlotinib inhibits EGFR (and possibly HER-2) (18) whilst sunitinib is a multiple receptor tyrosine kinase inhibitor.…”

Section: Introductionmentioning

confidence: 99%

The effect of a dimeric Affibody molecule (ZEGFR:1907)2 targeting EGFR in combination with radiation in colon cancer cell lines

et al. 2011

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Abstract. The epidermal growth factor receptor (EGFR) is frequently overexpressed in colorectal cancer and is therefore an attractive target for treatment. (Z EGFR:1907 ) 2 is a newly developed dimeric affibody molecule with high affinity to the extracellular part of EGFR. In this study, we evaluated the cytotoxic effects of (Z EGFR:1907 ) 2 in combination with external radiation and the possible inhibitory effects in the EGFR signalling pathways in the colon cancer cell lines HT-29 and HCT116. The effects were compared with an EGFR antibody (cetuximab) and the tyrosine kinase inhibitors (erlotinib and sunitinib). These cell lines are genotypically different with respect to e.g. KRAS and BRAF mutational status, recently shown to be of clinical significance for therapeutic effects. Both cell lines express approximately 100,000-150,000 EGFRs per cell but differ in the radiation response (HCT116, SF2=0.28 and HT-29, SF2=0.70). Exposure to (Z EGFR:1907 ) 2 produced a small, but significant, reduction in survival in HCT116 but did not affect HT-29 cells. Similar results were obtained after exposure to EGF and the EGFR antibody cetuximab. The EGFR tyrosine kinase targeting inhibitor erlotinib and the multi-tyrosine kinase inhibitor sunitinib reduced survival in both cell lines. However, none of the drugs had any significant radiosensitizing effects in combination with radiation. Akt and Erk are central proteins in the EGFR downstream signalling and in the cellular response to ionizing radiation. The activation of Akt (Ser 473) and Erk (Thr202/ Tyr204) by radiation was both dose-and time-dependent. However the activation of EGFR was not clearly affected by radiation. Neither (Z EGFR:1907 ) 2 nor any of the other drugs were able to completely inactivate Akt or Erk. On the contrary, erlotinib stimulated Akt phosphorylation in both cell lines and in HCT116 cells Erk was activated. Overall the results illustrate the complexity in response to radiation and drugs in cells with differential phenotypic status.

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“…Erbitux was approved by the US Food and Drug Administration (FDA) for use in combination with irinotecan for the treatment of metastatic colorectal cancer and it is also being used for the treatment of metastatic squamous cell carcinoma of the head and neck (SCCHN) (Wong, 2005). Results of a large phase II study on irinotecan-refractory, colorectal cancer patients have shown a significant response of 22.9% when Erbitiux was combined with chemotherapy agent, irinotecan (Cunningham et al, 2004).…”

Section: Pdt In Combination With Erbituxmentioning

confidence: 99%

Photodynamic Therapy in Combination with Antiangiogenic Approaches Improve Tumor Inhibition

Ramaswamy¹,

Olivo²,

Yuen³

et al. 2011

Current Cancer Treatment - Novel Beyond Conventional Approaches

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Cetuximab: An epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer

Cited by 217 publications

References 21 publications

Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

The effect of a dimeric Affibody molecule (ZEGFR:1907)2 targeting EGFR in combination with radiation in colon cancer cell lines

Photodynamic Therapy in Combination with Antiangiogenic Approaches Improve Tumor Inhibition

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