Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance

Despite advances in breast cancer diagnosis and treatment, many patients still fail therapy, resulting in disease progression, recurrence, and reduced overall survival. Historically, much focus has been put on the intrinsic subtyping based in the presence (or absence) of classical immunohistochemistry (IHC) markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-related protein (HER2). However, it is widely understood that tumors are composed of heterogeneous populations of cells with a hierarchical organization driven by cancer stem cells (CSCs). In breast tumors, this small population of cells displaying stem cell properties is known as breast CSCs (BCSCs). This rare population exhibit a CD44(+)/CD24(−/low) phenotype with high ALDH activity (ALDH(+)), and possesses higher tolerability to chemotherapy, hormone therapy, and radiotherapy and is able to reproduce the bulk of the tumor after reduction of cell populations sensitive to first-line therapy leading to disease relapse. In this review, we present special attention to BCSCs with future directions in the establishment of a therapy targeting this population. Drugs targeting the main BCSCs signaling pathways undergoing clinical trials are also summarized.