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Endocrine Resistance and Breast Cancer Stem Cells: The Inflammatory Connection that Could Lead to New and Improved Therapy Outcomes

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Resistance to Targeted Therapies in Breast Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 16))

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Abstract

Breast cancer is the most commonly diagnosed cancer among American women and claims over 40,000 lives each year. Nearly 75% of breast tumors express estrogen receptor (ER) and will be treated with endocrine therapy, such as tamoxifen or aromatase inhibitors. Interfering with ER action via endocrine therapies has been a mainstay of breast cancer treatment for more than a century. But despite its proven success, the onset of endocrine resistance limits its usefulness. It is estimated that up to 50% of ER+ tumors fail to respond to endocrine therapy and eventually recur as aggressive, metastatic cancers. Therapy failure and aggressive tumor phenotypes have been attributed to the presence of a therapy-resistant population of cells within the tumor called breast cancer stem cells (CSCs). Breast CSCs are a small subpopulation of highly tumorigenic cells with stem-like features that sit at the apex of the hierarchy to drive tumor initiation, growth, and progression. Like their normal counterparts, being able to self-renew and differentiate are two hallmarks of CSCs, which in turn drive tumorigenesis, contribute to heterogeneity, and are the seeds of recurrent tumors and distant metastasis. Thereby, targeting breast CSCs will sensitize resistant, aggressive tumors to therapy, and prevent future recurrence and metastasis. Given that the inflammatory nuclear factor κB (NFκB) pathway plays an essential role in regulating breast CSCs, NFκB pathway inhibition can be exploited to eradicate CSCs and potentially overcome endocrine resistance.

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Abbreviations

AF1, 2:

Function domain 1 and 2

AI:

Aromatase inhibitor

ALDH1:

Aldehyde dehydrogenase 1

AP-1:

Activator protein 1

CSC:

Cancer stem cell

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

ERE:

Estrogen response element

HER2:

Human epidermal growth factor receptor 2

IGF1R:

Insulin-like growth factor receptor

LBD:

Ligand-binding domain

NFκB:

Nuclear factor kappa B

SERD:

Selective estrogen receptor downregulator

SERM:

Selective estrogen receptor modulator

SP-1:

Specificity protein 1

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA

    Irida Kastrati

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  1. Irida Kastrati
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Correspondence to Irida Kastrati .

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  1. Harper Cancer Research Institute, University of Notre Dame, South Bend, Indiana, USA

    Jenifer R. Prosperi

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Kastrati, I. (2017). Endocrine Resistance and Breast Cancer Stem Cells: The Inflammatory Connection that Could Lead to New and Improved Therapy Outcomes. In: Prosperi, J. (eds) Resistance to Targeted Therapies in Breast Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-70142-4_3

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