Medicine in focusBreast cancer: The upgraded role of HER-3 and HER-4
Introduction
The hallmark of breast cancer is the great heterogeneity rendering its treatment complex. Certain clinical characteristics have been used to predict which patients are likely to have favourable or unfavourable course. Molecular prognostic and predictive factors have been also extensively evaluated to assist tailored treatment of breast cancer more than for any other solid tumour (Karamouzis et al., 2002). However, the development of optimal consensus treatment guidelines for breast cancer requires both the comprehensive analysis of the results of randomized clinical trials and the interpretation of their clinical and biological relevance for individual patients (Goldhirsch et al., 2005). Molecular markers of prognosis and prediction in breast cancer are still considered less than ideal (Hayes, 2005). Recently, major research efforts have focused on identifying novel valuable markers, expression profiles and/or genetic “fingerprints” that could potentate the efficacy of current and future treatment regimens.
Section snippets
The ErbB receptor family in breast cancer
The transmembrane receptors that bear tyrosine kinase (TK) activity play a key role in breast cancer. The type I TK receptor family comprises four homologous members: ErbB-1 [epidermal growth factor (EGF) receptor (EGFR) or HER-1], ErbB-2 (HER-2/neu), ErbB-3 (HER-3) and ErbB-4 (HER-4). All family members have intrinsic TK activity, except for HER-3 (Fig. 1). The phosphorylation of these receptors (evoked by ligand binding and homo-or heterodimerisation) ignites a cascade of signalling pathways
Therapy
In recent years, significant treatment advances parallel the increased detection of breast carcinomas in earlier and more curable stages. In conjunction to the refinement of conventional treatment modalities, the identification of HER-2 as an important regulator of breast cancer cell proliferation led to the development of strategies aiming at reducing HER-2 receptor levels or activity, with the more successful being trastuzumab. However, certain aspects related to trastuzumab await
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