HER Dysregulation in Cancer

Inappropriate activation of HER family receptors

In normal cells, the process of HER activation is closely regulated, keeping cell growth under control. In cancer, HER receptors may be inappropriately activated, leading to uncontrolled growth and spread of tumor cells.1

Overexpression of HER receptors can lead to increased signaling, and genetic mutations can lead to the production of HER receptors that can be activated even without ligand binding.2 When tumors express both HER family receptors and their associated ligands, an autocrine loop, in which the tumor stimulates its own growth, can result.1

HER dysregulation3

HER dysregulation image showing cell cycle control, angiogenesis, apoptosis

HER2 amplification and overexpression

Dysregulation of HER2 signaling in cancer involves an excess of signals that stimulate cancer cells to grow and spread.1,2,4,5 It is this excess of signals, rather than a mutation in the receptor itself, that results in the deleterious effects of HER2 in cancer. In fact, HER2 gene amplification and receptor overexpression occur in about 25% of breast cancers.6


  1. Prenzel N, Fischer OM, Streit S, et al. The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Relat Cancer. 2001;8:11-31. PMID: 11350724
  2. Ejskjaer K, Sørensen BS, Poulsen SS, et al. Expression of the epidermal growth factor system in endometrioid endometrial cancer. Gynecol Oncol. 2007;104:158-167. PMID: 16962163
  3. Ménard S, Tagliabue E, Campiglio M, Pupa SM. Role of HER2 gene overexpression in breast carcinoma. J Cell Physiol. 2000;281:150-162. PMID: 10623878
  4. Edwards J, Traynor P, Munro AF, Pirret CF, Dunne B, Bartlett JM. The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer. Clin Cancer Res. 2006;12:123-130. PMID: 16397033
  5. Baker CH, Pino MS, Fidler IJ. Phosphorylated epidermal growth factor receptor on tumor-associated endothelial cells in human renal cell carcinoma is a primary target for therapy by tyrosine kinase inhibitors. Neoplasia. 2006;8:470-476. PMID: 16820093
  6. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707-712. PMID: 2470152