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The role of targeted therapy in breast cancer.

In this issue, we focus on the importance of targeted therapy in breast cancer. In the first of our three features, Leary and Johnston discuss current understanding about reasons for failure of the most established and the first targeted treatment in cancer, namely endocrine therapy. The oestrogen receptor (ER) is fundamental to breast development and the cancers that arise therein. The different modes by which ERs can stimulate cell growth and how these may lead to endocrine therapy resistance are discussed clearly and succinctly. The role of membrane-associated growth factors, especially the human epidermal growth factor receptor (HER) family, and their relationships and interactions with the ER and their role in endocrine therapy resistance are among the better understood mechanisms of resistance. Understanding this and other resistance mechanisms such as ER loss or increase, hypersensitivity to oestrogens, mutations and drug metabolism would be of major importance clinically and could lead to further improvements on the established success of targeting the ER.

The importance of the HER2 pathway and its targeting has been a great triumph. Within two decades the pivotal role of HER2 in the aggressive behaviour of this type of breast cancer has been described, and effective treatment developed, tested and become standard of care in the adjuvant setting with the potential to save many thousands of lives. Crabb and Chia describe the current data on HER2-targeted therapies and explore some of the questions about the optimal use of trastuzumab in the adjuvant and metastatic breast cancer settings, as well as the areas where knowledge is lacking. They also discuss the data on second-generation agents against HER2, lapatinib and pertuzumab.

The requirement for new blood vessel development has long been recognised as a potential target for cancer therapy, as growth of a tumour beyond a few cells requires angiogenesis. Gillmore and Miles describe the progress in targeting angiogenesis in breast cancer. The clinical trial programme of the most advanced strategy of targeting vascular endothelial growth factor (VEGF) with the antibody bevacizumab as well as some of the small molecule multi-targeting agents is discussed.

Normal stem cell research has huge potential for advancing medicine on many fronts. In parallel, understanding cancer stem cells may allow major advances in understanding resistance to current treatment modalities and provide new targets for the future. Tumours in many tissues are now thought to develop from dysregulated stem or progenitor cells and these cancer stem cells may be recognised by cell surface protein expression. Howell et al., from one of the groups that has pioneered breast cancer stem cell research, describe the dysregulated pathways, such as the Notch signalling pathway, and the connection between Notch pathway activation of breast cancer stem cells, stem cell self-renewal pathways and how this might lead to novel therapeutic targets in both pre-invasive and invasive breast cancer. Selecting targets for treatment

Andrew Wardley

Christie Hospital, Manchester, UK
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Article Details
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Author:Wardley, Andrew
Publication:Advances in Breast Cancer
Article Type:Editorial
Geographic Code:4EUUK
Date:Jun 1, 2007
Next Article:Mechanisms of endocrine resistance.

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