Translational research of a novel humanized epidermal growth factor receptor-related protein: a putative inhibitor of pan-ErbB.

ABSTRACT

PURPOSE: The ErbB family members are protein tyrosine kinases, which play a crucial role in the signal transduction pathways that regulate key cellular functions. Overexpression of the ErbB family members is associated with oncogenicity, metastatic potential, cell proliferation, apoptosis, angiogenesis, and prognosis in cancer. Molecular-targeted therapies centered on the ErbB signaling pathway are the currently promising anti-cancer therapies. METHODS: We reviewed the literature to summarize the current knowledge of epidermal growth factor receptor (EGFR)-related protein (ERRP) and determine the potential of this protein to be translated into a molecular-targeting treatment for cancer. RESULTS: ERRP isolated from rat gastroduodenal mucosa is a pan-ErbB inhibitor that targets multiple members of the ErbB family both in vitro and in vivo. Sequestration of ErbB ligands by ERRP results in the formation of inactive ErbB heterodimers and subsequent attenuation of signaling pathways activated by ErbB. We suggest a strategy to develop a humanized ERRP protein based on activity of rat EERP in vitro. CONCLUSIONS: As rat ERRP protein is expected to generate an immune response in humans, we propose a hypothesis that a humanized version of ERRP has potential therapeutic value for cancer patients.