Understanding the HER family in breast cancer: interaction with ligands, dimerization and treatments

Breast carcinoma is the most frequent type of cancer affecting women. Among the recently described molecular and phenotypic classes of breast cancer, human epidermal growth factor receptor 2 (HER2)-positive tumours are associated with a poor prognosis. HER2 plays an important role in cancer progression being targeted to provide predictive and prognostic information. Moreover, HER2 is related to cancer resistance against a variety of therapies; however, trastuzumab (herceptin) has proved successful in treatment of this subgroup. Nevertheless, resistance to this drug may be acquired by patients after a period of treatment, which indicates that other molecular mechanisms might influence success of this therapy. Dimerization between members of the HER family may contribute to resistance against treatments due to different combinations that trigger different downstream pathways. This is promoted by ligands, which are expressed as transmembrane precursor protein molecules and have a conserved epidermal growth factor-like domain. Through resistance to trastuzumab, other drugs are being developed to interact in different domains of HER2 protein. It might be a good strategy to apply new drugs simultaneously to trastuzumab due to act in different domains of HER2. The study of interaction between receptors/ligands will characterize specifically their signalling pathway and understand which strategy to acquire.