Combined therapies for cancer: a review of EGFR-targeted monotherapy and combination treatment with other drugs

Abstract

Targeted therapy refers to anticancer treatment which specifically targets key molecules of cancer cells and/or neovascular cells, aiming to thus interfere with processes of tumorigenesis, cancer progression and metastasis. The epidermal growth factor receptor (EGFR) was the first receptor to be proposed for targeted cancer therapy, having been found to be commonly overexpressed in a range of solid tumors and play a role in cancer cell proliferation, apoptosis, angiogenesis, invasion and metastasis. Despite successful development of EGFR-targeted pharmacological agents, clinical and molecular studies have indicated several limitations to the broad application of this treatment as a monotherapy. Novel combination treatments which might optimize the effect of EGFR inhibition have, therefore, been investigated. Research conducted into the mechanisms of action and synergy of these combination treatments is likely to enhance the role of the EGFR target in future cancer treatment.

Fig. 1

EGF binding to EGFR and subsequent downstream signaling pathways (modified from Marshall 2006). Binding of EGF or EGF-like growth factor ligands to HER1/EGFR results in activation of three main pathways, promoting development of malignancy, tumor cell motility and metastasis, and angiogenesis (Yarden 2001). EGF epidermal growth factor, VEGF vascular endothelial growth factor, PDGF platelet-derived growth factor, IGF insulin-like growth factor, MAPK mitogen-activated protein kinase, ERK extracellular signal-regulated kinase, PI3K phosphatidylinositol 3-OH kinase, mTOR mammalian target of rapamycin, PTEN phosphatase and tensin homolog deleted from chromosome 10, JAK janus family kinase, STAT signal transducer and activator of transcription