Understanding the cancer stem cell phenotype: A step forward in the therapeutic management of cancer

Biochem Pharmacol. 2019 Apr:162:79-88. doi: 10.1016/j.bcp.2019.01.020. Epub 2019 Jan 25.

Abstract

The experimental validation of the existence of cancer stem cells (CSC) has had a significant impact on our understanding of the cellular mechanisms and signaling networks involved in the process of carcinogenesis and its progression. These findings provide insights into the critical role that tumor microenvironment and metabolism play in the acquisition of the drug resistance phenotype as well as provide potential targets for therapeutic exploitation. Here we briefly review the literature on the involvement of key signaling pathways such as Wnt/β-catenin, Notch, Hedgehog and STAT3 in the appearance of cancer cells with stem cells-like characteristics. In addition, we also highlight some of the recent therapeutic strategies used to target these pathways as well as approaches aiming to specifically target CSCs through their distinctive metabolic features.

Keywords: Cancer cell metabolism; Cancer stem cells; Drug resistance; Hedgehog; Notch; STAT3; Wnt/β-catenin.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Disease Management*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / physiology*
  • Phenotype*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / physiology*
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / physiology

Substances

  • Antineoplastic Agents