SIGNIFICANCE OF MEMBERS OF THE ERBB-GEN F AMILY FOR TUMOR-DEVELOPMENTAS PROGNOSTIC FACTORS AND FOR NOVEL THERAPEUTIC OPTIONS

RNA and DNA viruses can be transforming and tumourigenic agents. The t ransformation is a consequence of the ability of viruses to integrate into the host cell's DNA and to produce transforming proteins. These p roteins are mainly produced by specific integral parts of the viral ge nome, the oncogenes. Comparison between RNA/DNA sequence of viral onco genes and normal human genome of non-transformed cells revealed high s equence similarities in specific genomic areas, which were named cellu lar proto-oncogens. They are important components of the growth regula tory pathways in normal cells. The accumulation of genetic alterations of some proto-oncogens, like the erbB-family, may be part of the mech anism, by which malignant cells can acquire a selective growth advanta ge. 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 c an provide additional information on the disease-free survival and ove rall survival for patients with breast, ovarian, endometrial or cervic al cancer. Molecular and cell-physiological analyses have improved the understanding of tumour biology and provide the opportunity for new t herapeutic approaches. Monoclonal antibody targeted therapy directed a gainst EGF-R or Her-2/neu, the use of anti-sense oligonucleotides and oligodeoxynucleotides, and the application of tyrosine kinase and prot ein C-kinase inhibitors are currently being investigated.