Endocrine Resistance And Breast Cancer Invasion

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Stephen Hiscox, Julia Gee, and Robert I. Nicholson

Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Heath Park, Cardiff, CF10 3XF, UK

Abstract: Despite the initial success of endocrine therapies, a significant proportion of women will acquire resistance to such treatments. Furthermore, clinical relapse during anti-hormonal therapy has been linked to tumours that have gained an aggressive phenotype and enhanced metastatic capacity and is frequently associated with a poorer outlook for the patient. Recently, we have demonstrated that the acquisition of an endocrine resistant state in breast cancer cells is accompanied by a profound increase in invasive capacity. Tumour cell invasion is fundamental to the subsequent development of metastasis, the most significant factor that affects the survival of patients with cancer. Despite this, past therapeutic approaches have paid relatively little attention to these important issues; thus a greater understanding of this process will lead to the identification of potential targets for anti-invasive intervention for such patients. To this end, we are currently addressing potential mechanisms which may underlie such processes in acquired anti-hormone resistance and have identified several molecular elements through the study of cell models of acquired endocrine resistance.

Keywords: breast cancer; endocrine-resistance; invasion; EGFR; Src kinase; c-Met

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