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

Abstract

Over the last 15 years, basic science and clinical studies have been conducted to identify cancer stem cells (CSCs) in several types of cancer to reveal their mechanistic involvement in cancer recurrence for therapeutic exploitation. Exposure of cancer cells and tissues to hypoxia, or sub-atmospheric concentrations of oxygen (<21 % O 2 ), stimulates a variety of stress responses that bias the cells toward a self-preserving, anti-apoptotic phenotype, properties that are found in CSCs. Despite major advances in our understanding of hypoxia, CSCs, and their interrelated nature, some of the most promising cancer therapy has been of limited clinical efficacy, in part because of the inherently hypoxic nature of growing tumors. In this paper we discuss recent findings regarding the behavior of breast and brain CSCs under hypoxia, and the mechanisms of their chemo and/or radioresistance and metastatic potential.