The last 15 years have brought an understanding of growth and differentiation at the molecular
level expanding our knowledge of the origin and progression of cancer. Early breakthroughs
defining growth control pathways came via studies of oncogenes mutated signaling molecules
that have lost the capacity to tum off their proliferative signal. Oncogenes with diverse
growth-promoting activities have been discovered covering the gamut from cell surface to
nuclear signaling. Sequencing of these oncogenes revealed that they were mutated forms of
captured cellular genes and displayed tyrosine kinase activity. The epidermal growth factor
(EGF) receptor was the first of 40-50 transmembrane tyrosine kinase receptors to be cloned and
sequenced. Beyond cell proliferation activation of EGF receptor by its specific ligands
controls important physiological processes such as cell differentiation apoptosis cell
migration and cell shape. Activation of autocrine growth loops consisting in solid human
tumors of upregulated expression of EGFR together with increased production of ligands
suggested its crucial role in autonomous tumor growth.
