SIGNIFICANCE OF MEMBERS OF THE ERBB-GEN FAMILY FOR TUMOR-DEVELOPMENT AS PROGNOSTIC FACTORS AND FOR NOVEL THERAPEUTIC OPTIONS

RNA and DNA viruses can be transforming and tumourigenic agents. The transformation is a consequence of the ability of viruses to integrate into the host cell's DNA and to produce transforming proteins. These proteins are mainly produced by specific integral parts of the viral genome, the oncogenes. Comparison between RNA/DNA sequence of viral oncogenes and normal human genome of non-transformed cells revealed high sequence similarities in specific genomic areas, which were named cellular proto-oncogens. They are important components of the growth regulatory pathways in normal cells. The accumulation of genetic alterations of some proto-oncogens, like the erbB-family, may be part of the mechanism, by which malignant cells can acquire a selective growth advantage. The epidermal growth factor receptor (EGF-R, c-erbB1), Her-2/neu (c-erbB2), and c-erbB3 are members of the erbB-family. The detection of increased abundance of EGF-R or Her-2/neu proteins in human tumours can provide additional information on the disease-free survival and overall survival for patients with breast, ovarian, endometrial or cervical cancer. Molecular and cell-physiological analyses have improved the understanding of tumour biology and provide the opportunity for new therapeutic approaches. Monoclonal antibody targeted therapy directed against EGF-R or Her-2/neu, the use of anti-sense oligonucleotides and oligodeoxynucleotides, and the application of tyrosine kinase and protein C-kinase inhibitors are currently being investigated.