Epithelial growth factor receptor (EGFR) pathway and renal cell carcinoma

Abstract

The epidermal growth factor receptor (EGFR) pathway is a very well-known pathway implicated in proliferation, growth and metastatic development of various tumor types. Consequently, EGFR pathway inhibitors have provided clinical benefits in many tumor types. EGFR expression is reported in up to 95% of renal cell carcinoma (RCC) and is considered high (3+) in up to 60%. In preclinical models, the EGFR pathway appears implicated in tumor development. Its mode of action includes the common EGFR signal transduction cascades, but it also interacts with the angiogenic pathway, especially the vascular endothelial growth factor receptor (VEGFR) pathway. Monotherapy with EGFR pathway inhibitors does not appear to modify the history of metastatic RCC (MRCC) and does not justify further experiments in this setting. The issues now requiring attention are the degree to which the EGFR pathway is involved in RCC tumors expressing high EGFR levels—a phase III study suggests that it influences outcome in these patients—and the clinical benefit of associating antiangiogenic therapy and EGFR pathway inhibitors in the light of successive phases II trials. In conclusion, the EGFR pathway is probably not a major pathway in RCC development compared to the antiangiogenic pathways, but could play a role in association with antiangiogenics or in the event of progression after antiangiogenic therapy. Additional preclinical data is needed to support these hypotheses.