Cancer stem cells: Culprits in endocrine resistance and racial disparities in breast cancer outcomes.

Cancer Lett

Department of Basic Sciences, Loma Linda University Health School of Medicine, Loma Linda, CA, USA; Center for Health Disparities and Molecular Medicine, Loma Linda University Health School of Medicine, Loma Linda, CA, USA; Department of Pharmaceutical and Administrative Sciences, Loma Linda University Health School of Pharmacy, Loma Linda, CA, USA. Electronic address:

Published: March 2021

Breast cancer stem cells (BCSCs) promote endocrine therapy (ET) resistance, also known as endocrine resistance in hormone receptor (HR) positive breast cancer. Endocrine resistance occurs via mechanisms that are not yet fully understood. In vitro, in vivo and clinical data suggest that signaling cascades such as Notch, hypoxia inducible factor (HIF), and integrin/Akt promote BCSC-mediated endocrine resistance. Once HR positive breast cancer patients relapse on ET, targeted therapy agents such as cyclin dependent kinase inhibitors are frequently implemented, though secondary resistance remains a threat. Here, we discuss Notch, HIF, and integrin/Akt pathway regulation of BCSC activity and potential strategies to target these pathways to counteract endocrine resistance. We also discuss a plausible link between elevated BCSC-regulatory gene levels and reduced survival observed among African American women with basal-like breast cancer which lacks HR expression. Should future studies reveal a similar link for patients with luminal breast cancer, then the use of agents that impede BCSC activity could prove highly effective in improving clinical outcomes among African American breast cancer patients.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872014PMC
http://dx.doi.org/10.1016/j.canlet.2020.12.014DOI Listing

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