|Target of antibody|
|EGFR; Synonyms: C-erb, CG10079, D-EGFR, D-Egf, DEGFR, DER, DER flb, DER/EGFR, DER/faint little ball, DER/top, DER/torpedo, DER1, DEgfr, Degfr, Der, DmHD-33, Dmel\\CG10079, EFG-R, EGFr, EGfr, EK2-6, Egf, Egf-r, EgfR, El, Elp, Elp-1, Elp-B1, Elp-B1RB1, HD-33, TOP, Torpedo/DER, Torpedo/Egfr, c-erbB, d-egf-r, dEGFR, dEGFR1, dEgfr, der, egfr, flb, l(2)05351, l(2)09261, l(2)57DEFa, l(2)57EFa, l(2)57Ea, mor1, top, top/DER, top/flb, torpedo/Egfr, torpedo/egfr, EGFR12, EGFR15, egfr1, Erbb2, ERBB, ERBB1, HER1, PIG61, mENA, ErbB-1, Errp, 9030024J15Rik, AI552599, Erbb, Errb1, Wa5, wa-2, wa2
(Mechanism of action; Source EMA document)
|Cetuximab is a chimeric monoclonal IgG1 antibody that is specifically directed against the epidermal growth factor receptor (EGFR).
EGFR signalling pathways are involved in the control of cell survival, cell cycle progression, angiogenesis, cell migration and cellular invasion/metastasis.
Cetuximab binds to the EGFR with an affinity that is approximately 5- to 10-fold higher than that of endogenous ligands. Cetuximab blocks binding of endogenous EGFR ligands resulting in inhibition of the function of the receptor. It further induces the internalisation of EGFR, which can lead to downregulation of EGFR. Cetuximab also targets cytotoxic immune effector cells towards EGFRexpressing tumour cells (antibody dependent cell-mediated cytotoxicity, ADCC).
Cetuximab does not bind to other receptors belonging to the HER family. The protein product of the proto-oncogene RAS (rat sarcoma) is a central down-stream signal transducer of EGFR. In tumours, activation of RAS by EGFR contributes to EGFR-mediated increased proliferation, survival and the production of pro-angiogenic factors.
RAS is one of the most frequently activated family of oncogenes in human cancers. Mutations of RAS genes at certain hot-spots on exons 2, 3 and 4 result in constitutive activation of RAS proteins independently of EGFR signaling.