Breast cancer stem cells-from origins to targeted therapy

Abstract

Breast cancer is marked as one of the leading causes of malignancy-related morbidities worldwide. In spite of aggressive interventions, the inevitability of relapse and metastasis severely impede survival rates. Mounting evidence highlight the insidious role of cancer stem cells (CSCs), a small but significant subpopulation of undifferentiated cells that drive tumour progression, spread and resistance to conventional therapy. The nature and significance of breast CSCs remains poorly understood, and even disputed by many researchers. This review discusses the origins, biomarkers, signalling pathways, regulatory mechanisms, and targeted therapy of breast CSCs.

Keywords: Breast cancer stem cells (BCSCs); biomarkers; microRNAs; origins; regulatory mechanisms; signalling pathways; targeted therapy.

Figure 1

Models of BCSC formation. (A) Model 1: BCSCs originate from mammary stem cells. Several effective mutations that occurred during the quiescent state of stem cells initiate oncogenic transformation; (B) Model 2: BCSCs originate from mammary progenitor cells. Accumulation of multiple mutations at the level of transient amplifying progenitor cell leads to transformation and initiate malignancy; (C) Model 3: BCSCs originate from differentiated mammary cells. Differentiated cells are de-differentiated to re-acquire stem-cell properties. BCSC, breast cancer stem cell.