Biomarkers to Target Heterogeneous Breast Cancer Stem Cells

Breast cancer is the most common cancer and the second leading cause of death in U.S. women. Due to early detection and advanced treatment, the breast cancer death rate has been declining since 1990. However, disease recurrence is still the major obstacle in moving from therapy to truly curative treatments. Recent evidence has indicated that breast cancer recurrence is often caused by a subpopulation of breast cancer cells. This subset of cancer cells, usually referred to as breast cancer stem cells (BCSCs), exhibits stem cell phenotypes. They can self-renew and asymmetrically divide to more differentiated cancer cells. These cells are also highly resistant to conventional therapeutic reagents. Therefore, identifying and characterizing these BCSC subpopulations within the larger population of breast cancer cells is essential for developing new strategies to treat breast cancer and prevent recurrence. In this review article, we discuss the current proposed model for the origin of tumor heterogeneity, summarize the recent findings of cell surface and cytoplasmic markers for BCSC identification, review the regulatory mechanisms by which BCSCs maintain or non-cancer stem cells acquire BCSC characteristics, describe the proposed strategies to eliminate BCSCs, and highlight the current limitations and challenges to translate basic BCSC research to clinical application including establishment of clinical biomarkers and therapeutic treatments specifically targeting BCSCs.