Oncogenes and growth factors.

Certain polypeptide gene products regulate mitosis, differentiation, and other basic biologic functions of cells. These genes and their products are well preserved throughout evolution. Other sets of genes encode receptors for these polypeptides. Polypeptide growth factors can stimulate the cells that express receptors for them. Autocrine growth occurs when a cell produces a growth factor and also expresses receptors for it. When certain genes remain in a permanently switched-on position or are amplified, excessive amounts of growth factors are produced and receptor-positive cells continuously respond, thus achieving illegitimate growth advantage over other cells. Permanently switched-on and/or point-mutated receptor-encoding genes direct the synthesis of truncated receptors that do not need to capture their ligand for signaling receptor activation, thus their cells remain in a permanently activated state. When immortalization and/or malignant transformation results from these activities, the gene is recognized as a protooncogene-oncogene. Acutely transforming retroviruses contain close derivatives of these cellular genes (c-onc----v-onc) obtained through transduction. Genes encoding the synthesis of nontransforming growth factors (angiogenesis factors, colony-stimulating factors, interleukins, etc.) imitate protooncogenes in stimulating the growth and differentiation-dedifferentiation on nonimmortalized cells. Immortalized and malignantly transformed cells may retain receptors to regulatory growth factors that may induced differentiation and/or cessation of mitosis. Growth factors or receptors produced in excess by transformed cells may be neutralized by monoclonal antibodies (McAb) breaking the chain of autocrine or paracrine growth. Protooncogenes-oncogenes may be deactivated by biological response modifiers (dexamethasone, interferons, bacterial toxins, etc.). These interventions may lead to a new treatment modality for the malignant process.