Cancer Stem Cells Under Hypoxia as a Chemoresistance Factor in the Breast and Brain

Abstract

Over the last fifteen years, basic science and clinical studies have aimed to identify cancer stem cells (CSCs) in multiple types of cancer in order to unravel their mechanistic roles in cancer recurrence for therapeutic exploitation. Exposure of cells and tissues to hypoxia, or sub-atmospheric concentrations of oxygen (< 21% O2), stimulates various stress response pathways that bias the cells towards a self-preserving, anti-apoptotic phenotype. Despite major advances in our understanding of hypoxia, CSCs, and their interrelated nature, some of the most promising cancer therapies have shown limited efficacy in clinic for the past few years, in part due to the inherently hypoxic nature of growing tumors. In the present article, we discuss recent findings regarding the behavior of breast and brain CSCs under hypoxia, as well as the mechanisms that have been shown to drive their chemo-/radioresistance and metastatic potential.