Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance

Molecules. 2018 Aug 30;23(9):2193. doi: 10.3390/molecules23092193.

Abstract

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.

Keywords: BCSCs; BCSCs markers; breast cancer; resistance; targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor