TARGETING THE HER FAMILY RECEPTORS IN BREAST CANCER: A BRIEF INTRODUCTION Breast cancer (BC) is the most common cancer type occurring in women world-wide. During the last 25 years, the technological progress that has characterised both genetic and molecular biology has led to a greater understanding of the events underlying the normal tissue development as well as malignant transformation. This level of knowledge has enabled the identifi cation of molecular players responsible for cell growth, survival, motility, and transformation that may serve as therapeutic targets. The human epidermal growth factor family receptors (HER) have been proposed as a rationale target for cancer therapy. This family of receptors comprises four receptors: HER1, HER2, HER3, and HER4. All four receptors share an extracellular ligandbinding domain, a trans-membrane section, and an intracellular tyrosine-kinase domain. The binding of a ligand to the extracellular domain induces the formation of receptor homodimers or heterodimers, phosphorylation of key tyrosine residues of the kinase domain and consequent recruitment of molecular adaptors and effectors that start the downstream, signalling cascade. Key pathways activated by HER signalling include the RAS-RAF-MAP kinase and the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathways ( 1 ) involved in the control of several cellular processes such as apoptosis, migration, growth, adhesion, and differentiation (reviewed in ( 1 – 3 )). Deregulated HER signalling is associated with malignant transformation. HER signalling can be altered via a number of mechanisms ( 3 ) including ligand overexpression, overexpression of the normal or constitutively mutated HER receptor, and defective HER receptor internalisation degradation ( 3 ). HER2 is the preferred dimerisation partner for the other HER family receptors ( 4 ).