Development of an Anticancer Drug Using Erbb-2 Ligand-s

In the last decade we have come to understand that the growth of cancer cells, in general andof breast cancer in particular, depends, in many cases, upon growth factors that will bind to and activatetheir receptors. One of these growth factor receptors is the erbB-2 protein which plays an importantrole in the prognosis of breast cancer and is overexpressed in nearly 30% of human breast cancerpatients. While evidence accumulates to support the relationship between erbB-2 overexpression andpoor overall survival in breast cancer, understanding of the biological consequence(s) of erbB-2overexpression remains elusive. The novel discovery of the erbB-2 ligand (gp3O) has allowed theidentification of a number of related but distinct biological endpoints which appear responsive to signaltransduction through the erbB-2 receptor. These endpoints of growth, invasiveness, and differentiationhave clear implications for the emergence, maintenance and/or control of malignancy, and representestablished endpoints in the assessment of malignant progression in breast cancer. The availability ofgp3O full length cDNAs provides tools necessary to acquire a better understanding of the mechanismof action of the this ligands and the erbB-2 receptor in breast cancer. These studies are designed todefine the involvement of gp3O in breast cancer. Specifically, we will construct a ligand/toxin fusionprotein in order to determine the ability of gp30-Saporin (SAP) to inhibit tumor growth of breast cancercells in vivo.