Breast cancer stem cells and the challenges of eradication: a review of novel therapies

Breast cancer is a heterogeneous disease that accounts for 30% of all cancers diagnosed in women and over half a million deaths per year. Cancer stem cells (CSCs) make up a small subpopulation of cells within a tumor, are capable of self-renewal and, are responsible for tumor initiation, formation, and recurrence. Breast CSCs (BCSCs) have been the subject of concentrated research as potential targets for breast cancer therapies. Cell surface markers CD44+/CD24- have been established as minimum biomarkers for BCSCs and the upregulation of CD44 expression has been linked to tumor formation in numerous cancers. Additionally, the deregulation of Notch, Wnt/Frizzled/β-catenin, Hippo, and Hedgehog signaling pathways is believed to be responsible for the formation of CSCs and lead to tumor formation. Tumor heterogeneity is a key feature of therapy resistance and a major challenge. CSCs are predominantly senescent and inherently immune to chemotherapy drugs which rely on an overactive cell cycle. Current therapeutic strategies include targeting CSC signaling pathways that play critical roles in self-renewal and defense. Anti-CD44 antibodies have been shown to induce terminal differentiation in CSCs resulting in a significant decrease in tumor metastasis. Additionally, targeting the tumor microenvironment has been shown to increase the effectiveness of chemotherapy drugs. In this review, we attempt to provide an overview of breast cancer, the stem of its cause, and novel therapies currently being explored.