scholarly journals The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1028 ◽  
Author(s):  
David Rodriguez ◽  
Marc Ramkairsingh ◽  
Xiaozeng Lin ◽  
Anil Kapoor ◽  
Pierre Major ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Estrogen Receptor ◽  
Cancer Stem Cells ◽  
Hormone Therapy ◽  
Endocrine Therapy ◽  
Endocrine Resistance ◽  
Therapy Resistance ◽  
Breast Cancer Stem Cells ◽  
Er Positive

Breast cancer stem cells (BCSC) play critical roles in the acquisition of resistance to endocrine therapy in estrogen receptor (ER)-positive (ER + ve) breast cancer (BC). The resistance results from complex alterations involving ER, growth factor receptors, NOTCH, Wnt/β-catenin, hedgehog, YAP/TAZ, and the tumor microenvironment. These mechanisms are likely converged on regulating BCSCs, which then drive the development of endocrine therapy resistance. In this regard, hormone therapies enrich BCSCs in ER + ve BCs under both pre-clinical and clinical settings along with upregulation of the core components of “stemness” transcriptional factors including SOX2, NANOG, and OCT4. SOX2 initiates a set of reactions involving SOX9, Wnt, FXY3D, and Src tyrosine kinase; these reactions stimulate BCSCs and contribute to endocrine resistance. The central contributions of BCSCs to endocrine resistance regulated by complex mechanisms offer a unified strategy to counter the resistance. ER + ve BCs constitute approximately 75% of BCs to which hormone therapy is the major therapeutic approach. Likewise, resistance to endocrine therapy remains the major challenge in the management of patients with ER + ve BC. In this review we will discuss evidence supporting a central role of BCSCs in developing endocrine resistance and outline the strategy of targeting BCSCs to reduce hormone therapy resistance.

scholarly journals Breast Cancer Stem Cells and Their Role in Resistance to Endocrine Therapy

2011 ◽  
Vol 2 (2) ◽  
pp. 91-103 ◽  
Author(s):  
Ciara S. O’Brien ◽  
Gillian Farnie ◽  
Sacha J. Howell ◽  
Robert B. Clarke
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Endocrine Therapy ◽  
Breast Cancer Stem Cells

scholarly journals miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance

2015 ◽  
Vol 6 (7) ◽  
pp. e1823-e1823 ◽  
Author(s):  
A De Cola ◽  
S Volpe ◽  
M C Budani ◽  
M Ferracin ◽  
R Lattanzio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Targeted Therapy ◽  
Cancer Stem Cells ◽  
Therapy Resistance ◽  
Breast Cancer Stem Cells

Resistance to Endocrine Therapy: Are Breast Cancer Stem Cells the Culprits?

2009 ◽  
Vol 14 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Ciara S. O’Brien ◽  
Sacha J. Howell ◽  
Gillian Farnie ◽  
Robert B. Clarke
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Endocrine Therapy ◽  
Breast Cancer Stem Cells

Estrogen receptor of breast cancer stem cells depending on the original breast cancers

2011 ◽  
Vol 77 (1) ◽  
pp. 71-73 ◽  
Author(s):  
Wei-Ru Xu ◽  
Hong-Sheng Lin ◽  
Xin-Yi Chen ◽  
Ying Zhang
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Estrogen Receptor ◽  
Cancer Stem Cells ◽  
Breast Cancer Stem Cells ◽  
Breast Cancers

scholarly journals Update on the Role of NFκB in Promoting Aggressive Phenotypes of Estrogen Receptor–Positive Breast Cancer

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
Emily Smart ◽  
Svetlana E Semina ◽  
Jonna Frasor
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Signaling Pathway ◽  
Endocrine Resistance ◽  
Dimethyl Fumarate ◽  
Therapy Resistance ◽  
Molecular Characteristics ◽  
Breast Cancers ◽  
Estrogen Receptor Positive

Abstract The majority of breast cancers are diagnosed as estrogen receptor–positive (ER+) and respond well to ER-targeted endocrine therapy. Despite the initial treatability of ER+ breast cancer, this subtype still accounts for the majority of deaths. This is partly due to the changing molecular characteristics of tumors as they progress to aggressive, metastatic, and frequently therapy resistant disease. In these advanced tumors, targeting ER alone is often less effective, as other signaling pathways become active, and ER takes on a redundant or divergent role. One signaling pathway whose crosstalk with ER has been widely studied is the nuclear factor kappa B (NFκB) signaling pathway. NFκB is frequently implicated in ER+ tumor progression to an aggressive disease state. Although ER and NFκB frequently co-repress each other, it has emerged that the 2 pathways can positively converge to play a role in promoting endocrine resistance, metastasis, and disease relapse. This will be reviewed here, paying particular attention to new developments in the field. Ultimately, finding targeted therapies that remain effective as tumors progress remains one of the biggest challenges for the successful treatment of ER+ breast cancer. Although early attempts to therapeutically block NFκB activity frequently resulted in systemic toxicity, there are some effective options. The drugs parthenolide and dimethyl fumarate have both been shown to effectively inhibit NFκB, reducing tumor aggressiveness and reversing endocrine therapy resistance. This highlights the need to revisit targeting NFκB in the clinic to potentially improve outcome for patients with ER+ breast cancer.

scholarly journals LPA/PKD-1 signaling promotes development of arteriolar niche that supports self-renewal of breast cancer stem cells and stemness

2020 ◽  
Author(s):  
Yinan Jiang ◽  
Yichen Guo ◽  
Jinjin Hao ◽  
Rachael Guenter ◽  
Justin Lathia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Estrogen Receptor ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Regulatory Mechanisms ◽  
Cancer Growth ◽  
Breast Cancer Stem Cells ◽  
Self Renewal ◽  
Estrogen Receptor Positive

ABSTRACTBreast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. However, the regulatory mechanisms of self-renewal and interactions with the vascular niche within tumor microenvironment are currently under investigation. Here, we demonstrate that BCSCs are enriched within arteriolar niche within the tumor microenvironment of estrogen receptor positive (ER+) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the LPA/PKD-1 signaling pathway, which promotes arteriolar differentiation and self-renewal. Furthermore, this pathway directly promotes stemness features. These findings suggest that targeting LPA/PKD-1 signaling may disrupt the arteriolar niche within the tumor microenvironment and concomitantly eradicate BCSCs, thereby attenuating BC progression.

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