eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
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10/2007
vol. 11
 
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Resistance to hormonotherapy in patients with breast cancer – molecular mechanisms and clinical implications

Anna Niwińska
,
Maria Litwiniuk

Współczesna Onkologia (2007) vol. 11; 10 (469–474)
Online publish date: 2008/01/30
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Endocrine resistance de novo occurs at first exposure to hormonal treatment and acquired resistance develops over time after an initial response to endocrine therapy. The explanation of this phenomenon is that over time breast cancer cells utilize alternative intracellular signalling pathways to enhance and activate oestrogen receptors (ER), which then allow cells to escape from their initial response to endocrine therapy. Data suggest that endocrine resistance may involve bi-directional interaction between ER and growth factor signalling, either via nongenomic ER activation of growth factor receptors at the plasma membrane or via intracellular activation of classical genomic ER in the nucleus by various intracellular kinases. In the presence of bi-directional cross-talk between ER and growth factor pathways, both tamoxifen and oestrogen function as agonist ligands. Identification of the key mechanisms could enable prediction of the response or resistance to hormonal therapy and the use of agents targeted at the various molecular components of endocrine resistance pathways.
keywords:

breast cancer, hormonotherapy, SERM, aromatase inhibitors, resistance

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