Targeting epidermal growth factor receptor signaling: early results and future trends in oncology

Abstract

Epidermal growth factor receptor (EGFR), a member of a family of membrane receptors with tyrosine kinase activity, is emerging as a target candidate for anti-cancer therapy, due to its overexpression in many carcinomas and its relationship with several hallmark properties of malignant behavior such as continuous cell proliferation, escape from apoptosis, cell migration and angiogenesis. Specially appealing is the overexpression of EGFR in tumors such as lung, colon, kidney and head and neck carcinomas which are mostly resistant to current chemotherapy. Several anti-EGFR agents are already in clinical testing: small molecule tyrosine kinases inhibitors, monoclonal antibodies and cancer vaccines. Early results provide evidence of antitumor activity in humans, to be confirmed in larger trials. Toxicity profiles do not overlap with chemotherapy or radiotherapy, but skin rash and diarrhea can be severe. Future investigations should clarify optimal schedules and explore combinations with standard onco-specific treatments. The ultimate challenge will be to combine diverse therapeutic interventions dealing with a regulatory system which is complex, highly redundant and robust. Combinations between vaccines and antibodies, or between vaccines to several molecular components of the system should be evaluated, as well as combinations between inhibitors of the EGFR signaling pathway and inhibitors of other regulatory pathways related to cell proliferation, apoptosis and angiogenesis.