Breast cancer stem cells and their role in resistance to endocrine therapy.
AffiliationSchool of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, M20 4BX, UK.
MetadataShow full item record
AbstractDevelopmentally, tumours can be viewed as aberrant versions of normal tissues. For example, tumours often retain differentiation markers of their tissue of origin. In addition, there is evidence that they contain cancer stem-like cells (CSCs) that drive tumourigenesis. In this review, we summarise current evidence that breast CSCs may partially explain endocrine resistance in breast cancer. In normal breast, the stem cells are known to possess a basal phenotype and to be mainly oestrogen receptor-α-negative (ER-). If the hierarchy in breast cancer reflects this, the breast CSC may be endocrine resistant because it expresses very little ER and can only respond to treatment by virtue of paracrine signalling from neighbouring, differentiated ER+ tumour cells. Normal breast epithelial stem cells are regulated by the epidermal growth factor receptor and other growth factor receptor signals. The observed increase in growth factor receptor expression in endocrine-resistant breast cancers may reflect a bigger proportion of CSCs selected by endocrine therapies. There is evidence from a number of studies that breast CSCs are ER- and EGR+/HER2+, which would support this view. It is reported that CSCs express mesenchymal genes, which are suppressed by ER expression, further indicating the mutual exclusion between ER+ cells and the CSCs. As we learn more about CSCs, differentiation and the expression and functional activity of the ER in these cells in diverse breast tumour sub-types, it is hoped that our understanding will lead to new modalities to overcome the problem of endocrine resistance in the clinic.
CitationBreast cancer stem cells and their role in resistance to endocrine therapy. 2011, 2 (2):91-103 Horm Cancer
JournalHormones & Cancer
- Resistance to endocrine therapy: are breast cancer stem cells the culprits?
- Authors: O'Brien CS, Howell SJ, Farnie G, Clarke RB
- Issue date: 2009 Mar
- FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4.
- Authors: McClements L, Annett S, Yakkundi A, O'Rourke M, Valentine A, Moustafa N, Alqudah A, Simões BM, Furlong F, Short A, McIntosh SA, McCarthy HO, Clarke RB, Robson T
- Issue date: 2019 Apr 11
- PAK4 regulates stemness and progression in endocrine resistant ER-positive metastatic breast cancer.
- Authors: Santiago-Gómez A, Kedward T, Simões BM, Dragoni I, NicAmhlaoibh R, Trivier E, Sabin V, Gee JM, Sims AH, Howell SJ, Clarke RB
- Issue date: 2019 Aug 28
- Basal/HER2 breast carcinomas: integrating molecular taxonomy with cancer stem cell dynamics to predict primary resistance to trastuzumab (Herceptin).
- Authors: Martin-Castillo B, Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Moreno JM, Corominas-Faja B, Urruticoechea A, Martín ÁG, López-Bonet E, Menendez JA
- Issue date: 2013 Jan 15
- Oestrogen increases the activity of oestrogen receptor negative breast cancer stem cells through paracrine EGFR and Notch signalling.
- Authors: Harrison H, Simões BM, Rogerson L, Howell SJ, Landberg G, Clarke RB
- Issue date: 2013 Mar 8