Epidermal growth factor in clinical practice - a review of its biological actions, clinical indications and safety implications

Abstract

Chemotaxis, mitogenesis, motogenesis and cytoprotection are common cellular events involved in both tumourigenesis and tissue repair, which appear amplified upon growth factors exposure. Epidermal growth factor (EGF) promotes these events in epithelial and mesenchymal cells through the binding to a specific tyrosine kinase receptor. In experimental oncology settings, EGF does not initiate malignant transformation but exhibits 'tumour promotion'. These observations have raised doubts on the clinical use of EGF despite solid demonstrations of efficacy in experimental conditions and clinical trials. The results of a Pubmed and Bioline investigation on EGF clinical uses and preclinical safety data are presented here. EGF topical administration has been used since 1989 to enhance the healing process of a variety of peripheral tissues wounds (16 clinical reports), as well as its intravenous, oral and rectal administration for gastrointestinal damages (11 clinical reports). EGF therapeutic efficacy and excellent tolerability seem demonstrated. Lack of long-term adverse effects is highlighted in those studies with 6, 12 and 24 months of patients follow-up. Although post-treatment follow-up may fall short for malignant growth, there are no reports on evidences linking EGF clinical use with cancer. A multicentre, nationwide survey in Cuba, 15 years after randomly using silver sulphadiazine with EGF or not in burn victims yielded that cancer incidence was comparable between EGF-treated and control subjects and that such incidence rate does not differ from the age-matched national incidence for those 15-year period. All the animal species subjected to long-term EGF systemic administration exhibit dose-dependent and reversible epithelial organs hyperplasia with no changes in cells phenotypic differentiation. Histotypic pre-malignant markers were not identified. The results emerged from co-carcinogenesis studies and from transgenic mice over-expressing EGF are conflicting and indicate that EGF overexposure, either innate or postnatal, may not be sufficient to transform cells. The ability of EGF to heal injured tissues in life-threatening scenarios or to assist in preventing physical and social disability advocates for its clinical use under a rational medical risk/benefit balance.