The Relationship between Ferroptosis and Tumors: A Novel Landscape for Therapeutic Approach

Curr Gene Ther. 2019;19(2):117-124. doi: 10.2174/1566523219666190628152137.

Abstract

Background: Ferroptosis is a newly discovered form of iron-dependent oxidative cell death characterized by lethal accumulation of lipid-based reactive oxygen species (ROS). It is distinct from other forms of cell death including apoptosis, necrosis, and autophagy in terms of morphology, biochemistry and genetics.

Discussion: Ferroptosis can be induced by system xc- inhibitors or glutathione peroxidase 4 (GPx4) inhibitors, as well as drugs such as sorafenib, sulfasalazine (SAS), and artesunate (ART). Ferroptosis has been recently shown to be critical in regulating growth of tumors, such as hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic carcinoma, and diffuse large B cell lymphoma (DLBCL). Ferroptosis is also associated with resistance to chemotherapeutic drugs and the anti-tumor efficacy of immunotherapy.

Conclusion: This review summarizes the mechanism of ferroptosis and its relationship with different types of tumors, to advance our understanding of cell death and to find a novel approach for clinical cancer management.

Keywords: Ferroptosis; ROS; cancer; chemotherapeutic drug resistance therapeutic approach; iron metabolism..

Publication types

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

MeSH terms

  • Apoptosis / genetics
  • Artesunate / therapeutic use
  • Autophagy / genetics*
  • Cell Death / genetics
  • Ferroptosis / drug effects
  • Ferroptosis / genetics*
  • Humans
  • Iron / metabolism
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Phospholipid Hydroperoxide Glutathione Peroxidase / genetics
  • Reactive Oxygen Species / metabolism
  • Sulfasalazine / therapeutic use

Substances

  • Reactive Oxygen Species
  • Sulfasalazine
  • Artesunate
  • Iron
  • Phospholipid Hydroperoxide Glutathione Peroxidase