Breast cancer stem cell: the roles and therapeutic implications

Cell Mol Life Sci. 2017 Mar;74(6):951-966. doi: 10.1007/s00018-016-2334-7. Epub 2016 Aug 16.

Abstract

Breast cancers have been increasingly recognized as malignancies displaying frequent inter- and intra-tumor heterogeneity. This heterogeneity is represented by diverse subtypes and complexity within tumors, and impinges on response to therapy, metastasis, and prognosis. Cancer stem cells (CSCs), a subpopulation of cancer cells endowed with self-renewal and differentiation capacity, have been suggested to contribute to tumor heterogeneity. The CSC concept posits a hierarchical organization of tumors, at the apex of which are stem cells that drive tumor initiation, progression, and recurrence. In breast cancer, CSCs have been proposed to contribute to malignant progression, suggesting that targeting breast cancer stem cells (BCSCs) may improve treatment efficacy. Currently, several markers have been reported to identify BCSCs. However, there is objective variability with respect to the frequency and phenotype of BCSCs among different breast cancer cell lines and patients, and the regulatory mechanisms of BCSCs remain unclear. In this review, we summarize current literature about the diversity of BCSC markers, the roles of BCSCs in tumor development, and the regulatory mechanisms of BCSCs. We also highlight the most recent advances in BCSC targeting therapies and the challenges in translating the knowledge into clinical practice.

Keywords: Biomarker; Epithelial–mesenchymal transition; Microenvironment; Signal pathway; Therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Models, Biological
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*

Substances

  • Biomarkers, Tumor