EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab

Abstract

Chemotherapy alone has limited ability to significantly improve survival in non-small lung cancer (NSCLC) beyond what has already been achieved. The epidermal growth factor (EGF) pathway plays a vital role in the pathogenesis and progression of NSCLC. Two classes of drugs inhibit the EGF receptor (EGFR) pathway: small molecules that inhibit the intracellular tyrosine kinase activity of the receptor, and monoclonal antibodies that target the extracellular domain in the ligand-binding region. Cetuximab is a human - mouse chimeric immunoglobulin G1 class monoclonal antibody directed against EGFR. Preclinical studies with cetuximab suggested that there was inhibition of growth of human NSCLC cell lines. Cetuximab is currently the focus of intense investigation in various patient populations with NSCLC. This review focuses on clinical trials of cetuximab in NSCLC and identifies future directions with this agent.

Keywords: EGFR; cetuximab; monoclonal antibodies; non-small cell lung cancer.

Figure 1

EGFR signaling pathway. The figure depicts the downstream pathways following activation of the EGF receptor. Binding of a ligand to the receptor activates the tyrosine kinase (K) which then activates the downstream signaling pathways that eventually lead to increased proliferation, cell cycle progression and decreased apoptosis. Solid arrows indicate stimulation, while dashed arrows indicate suppression. Sites of action of the tyrosine kinase inhibitors (TKIs) and monoclonal antibodies are also shown. Abbreviations: EGFR, endothelial growth factor receptor; PI3K, phosphoinositide-3-kinase; STAT, signal transducer and activator of transcription; JAK, Janus kinase; pAKT, phospho AKT; MAPK, mitogen-activated protein kinase.