The ErbB/HER family of receptor tyrosine kinases: A potential target for chemoprevention of epithelial neoplasms.

Abstract

Cancer chemoprevention trials can be directed at targeting established molecular mechanisms which contribute to neoplasia. One potential target is the ErbB/HER family of growth factor receptors with intrinsic tyrosine kinase activity. This group of four receptors mediates the action of multiple stromal ligands of the EGF/neuregulin family on the adjacent epithelium. Aberrant autocrine loops and overexpression of certain receptors, especially ErbB-2 (also called HER2 or Neu), play a role in fixation and propagation of oncogenic mutations. Here we concentrate on ErbB-2 and epithelial cancer and discuss current and future therapeutic strategies that may limit cancer, particularly in patients who are at high risk after removal of the primary tumor. Because ErbB-2 acts as a shared co-receptor, and its heterodimers are relatively potent receptor combinations, it offers selectivity that spares other routes of signal transduction. Immunotherapy, as well as gene therapy and tyrosine kinase inhibitors specific to ErbB-2 may join the ranks of effective chemopreventive agents.