ErbB Targeted Drugs and Angiogenesis

Erika      Iivanainen; Klaus      Elenius

doi:10.2174/157016110791112241

Abstract

Members of the ErbB receptor tyrosine kinase family are central regulators of several normal as well as tumor cell functions. A number of therapeutic compounds such as small molecular weight tyrosine kinase inhibitors and monoclonal antibodies have been developed to inhibit ErbB signaling in cancer. Drugs that target epidermal growth factor receptor (EGFR = ErbB1) and/or ErbB2 have demonstrated effect against breast, colorectal, lung, pancreatic and head and neck carcinomas, and are currently in clinical use. Part of the anti-tumor effect of the ErbB inhibitor drugs has been suggested to derive from inhibition of tumor angiogenesis. There are several proposed mechanisms by which the ErbB inhibiting agents may regulate tumor neovascularization although most of them are currently not fully characterized. This review addresses the role of ErbB signaling in angiogenesis, as well as the anti-angiogenic mechanisms of ErbB targeted cancer drugs.

Keywords: Anti-angiogenic drugs, cancer, EGFR, endothelial cells, HER, monoclonal antibodies, pericytes, smooth muscle cells, tyrosine kinase inhibitors