Extending aromatase inhibitor sensitivity in hormone resistant breast cancer
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Angela M.H. Brodie
,
Saranya Chumsri
Abstract
Aromatase inhibitors (AIs) are first-line treatment for ER+ breast cancer. However, despite responses initially, some patients can eventually acquire resistance. Moreover, 25% of all breast cancer patients do not express the estrogen receptor (ERα) and are innately resistance. In tumors of mouse models with acquired AI letrozole resistance, expression of ERα was reduced whereas HER2/growth factor signaling was enhanced. Treatment of mice with trastuzumab (HER2 antibody) reduced HER2/p-MAPK but restored ERα expression. The addition of trastuzumab to letrozole treatment when tumors progressed resulted in significantly longer tumor suppression than these drugs alone. Thus, inhibition of both HER2 and ERα signaling pathways was necessary to overcome resistance. In ERα-negative tumors, the receptor has been shown to be silenced by epigenetic modifications. Treatment of MDA-MB-231 ER-negative tumors with a histone deacetylase inhibitor, entinostat (ENT) increased expression of ERα and also aromatase. When ENT was combined with letrozole, tumor growth rate was markedly reduced compared with control tumors. ENT plus letrozole treatment also prevented the colonization and growth of MDA-MB-231 cells in the lung with significant reduction in visible and microscopic foci. These novel strategies could improve treatment for patients with acquired and innate resistance to AIs.
©2011 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Hormones in endocrine cancers
- Exposure to the endocrine disruptor bisphenol A alters susceptibility for mammary cancer
- Crosstalk with insulin and dependence on PI3K/Akt/mTOR rather than MAPK pathways in upregulation of basal growth following long-term oestrogen deprivation in three human breast cancer cell lines
- Antihormone induced compensatory signalling in breast cancer: an adverse event in the development of endocrine resistance
- The thyroid hormone receptors as tumor suppressors
- The role of nuclear endothelial nitric oxide synthase in the endothelial and prostate microenvironments
- Extending aromatase inhibitor sensitivity in hormone resistant breast cancer
- Benefits and risks during HRT: main safety issue breast cancer
- The antihormonal preventive therapy of breast cancer and prostate cancer
- A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR)
