Resistance to endocrine therapy: are breast cancer stem cells the culprits?

2.50
Hdl Handle:
http://hdl.handle.net/10541/69760
Title:
Resistance to endocrine therapy: are breast cancer stem cells the culprits?
Authors:
O'Brien, Ciara S; Howell, Sacha J; Farnie, Gillian; Clarke, Robert B
Abstract:
From a developmental point of view, tumors can be seen as aberrant versions of their tissue of origin. For example, tumors often partially retain differentiation markers of their tissue of origin and there is evidence that they contain cancer stem cells (CSCs) that drive tumorigenesis. In this review, we summarise current evidence that breast CSCs may partly explain endocrine resistance in breast cancer. In normal breast, the stem cells are known to possess a basal phenotype and to be mainly ERalpha-. If the hierarchy in breast cancer reflects this, the breast CSC may be endocrine resistant because it expresses very little ERalpha and can only respond to treatment by virtue of paracrine influences of neighboring, differentiated ERalpha+ tumor cells. Normal breast epithelial stem cells are highly dependent on the EGFR and other growth factor receptors and it may be that the observed increased growth factor receptor expression in endocrine-resistant breast cancers reflects an increased proportion of CSCs selected by endocrine therapies. There is evidence from a number of studies that breast CSCs are ERalpha- and EGFR+/HER2+, which would support this view. CSCs also express mesenchymal genes which are suppressed by ERalpha expression, further indicating the mutual exclusion between ERalpha+ cells and the CSCs. As we learn more about CSCs, differentiation and the expression and functional activity of the ERalpha in these cells in diverse breast tumor sub-types, it is hoped that our understanding will lead to new modalities to overcome the problem of endocrine resistance in the clinic.
Affiliation:
Breast Biology Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
Citation:
Resistance to endocrine therapy: are breast cancer stem cells the culprits? 2009, 14 (1):45-54 J Mammary Gland Biol Neoplasia
Journal:
Journal of Mammary Gland Biology and Neoplasia
Issue Date:
Mar-2009
URI:
http://hdl.handle.net/10541/69760
DOI:
10.1007/s10911-009-9115-y
PubMed ID:
19252972
Type:
Article
Language:
en
ISSN:
1573-7039
Appears in Collections:
All Paterson Institute for Cancer Research; Breast Biology

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Brien, Ciara S-
dc.contributor.authorHowell, Sacha J-
dc.contributor.authorFarnie, Gillian-
dc.contributor.authorClarke, Robert B-
dc.date.accessioned2009-06-05T10:10:21Z-
dc.date.available2009-06-05T10:10:21Z-
dc.date.issued2009-03-
dc.identifier.citationResistance to endocrine therapy: are breast cancer stem cells the culprits? 2009, 14 (1):45-54 J Mammary Gland Biol Neoplasiaen
dc.identifier.issn1573-7039-
dc.identifier.pmid19252972-
dc.identifier.doi10.1007/s10911-009-9115-y-
dc.identifier.urihttp://hdl.handle.net/10541/69760-
dc.description.abstractFrom a developmental point of view, tumors can be seen as aberrant versions of their tissue of origin. For example, tumors often partially retain differentiation markers of their tissue of origin and there is evidence that they contain cancer stem cells (CSCs) that drive tumorigenesis. In this review, we summarise current evidence that breast CSCs may partly explain endocrine resistance in breast cancer. In normal breast, the stem cells are known to possess a basal phenotype and to be mainly ERalpha-. If the hierarchy in breast cancer reflects this, the breast CSC may be endocrine resistant because it expresses very little ERalpha and can only respond to treatment by virtue of paracrine influences of neighboring, differentiated ERalpha+ tumor cells. Normal breast epithelial stem cells are highly dependent on the EGFR and other growth factor receptors and it may be that the observed increased growth factor receptor expression in endocrine-resistant breast cancers reflects an increased proportion of CSCs selected by endocrine therapies. There is evidence from a number of studies that breast CSCs are ERalpha- and EGFR+/HER2+, which would support this view. CSCs also express mesenchymal genes which are suppressed by ERalpha expression, further indicating the mutual exclusion between ERalpha+ cells and the CSCs. As we learn more about CSCs, differentiation and the expression and functional activity of the ERalpha in these cells in diverse breast tumor sub-types, it is hoped that our understanding will lead to new modalities to overcome the problem of endocrine resistance in the clinic.en
dc.language.isoenen
dc.subjectStem Cellsen
dc.subjectEstrogen Receptoren
dc.subjectProgesterone Receptoren
dc.subjectEndocrine Resistanceen
dc.titleResistance to endocrine therapy: are breast cancer stem cells the culprits?en
dc.typeArticleen
dc.contributor.departmentBreast Biology Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.en
dc.identifier.journalJournal of Mammary Gland Biology and Neoplasiaen

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