Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy

Abstract

SummaryThe epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor involved in the proliferation and survival of cancer cells. EGFR is the first molecular target against which monoclonal antibodies (mAb) have been developed for cancer therapy. Here we review the mechanisms underlying the effects of EGFR-specific mAb in cancer therapy. The efficacy of EGFR-specific mAb in cancer occurs thanks to inhibition of EGFRgenerated signalling; furthermore, the effects of antibodies on the immune system seem to play an important role in determining the overall anti-tumour response. In this review, attention is focused on cetuximab and panitumumab, two mAb introduced recently into clinical practice for treatment of metastatic colorectal and head and neck cancer which target the external part of EGFR.

Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

“…Cetuximab is a monoclonal IgG1 antibody directed against the epidermal growth factor receptor (EGFR) (Martinelli et al, 2009). Cetuximab binds to the extracellular domain of EGFR in its inactive configuration and competes for receptor binding by occluding the ligand-binding region.…”

Molecular Basis of Modern Targeted Therapy for Squamous Cell Carcinoma of the Tongue and Oral Mucosa With Monoclonal Antibodies

“…5). Клинические испытания нимотузумаба на больных ПРГШ свидетельствуют о значительном увеличении про-должительности жизни этих больных при введении высо-ких доз антитела в сочетании с радиотерапией [42].…”

Towards novel paradigms for cancer therapy

“…Epidermal growth factor receptor was the first molecular target for which monoclonal antibody (cetuximab) was developed for cancer therapy. The interaction with cetuximab promotes receptor internalization and degradation, thus blocking downstream signaling pathways involved in cell proliferation/differentiation, invasion, angiogenesis and apoptosis (Masui et al, 1986;Martinelli et al, 2009). Cetuximab has been already approved for treatment of advanced head and neck squamous cell carcinoma and metastatic colorectal carcinoma.…”