Cancer drug resistance: redox resetting renders a way

Oncotarget. 2016 Jul 5;7(27):42740-42761. doi: 10.18632/oncotarget.8600.

Abstract

Disruption of redox homeostasis is a crucial factor in the development of drug resistance, which is a major problem facing current cancer treatment. Compared with normal cells, tumor cells generally exhibit higher levels of reactive oxygen species (ROS), which can promote tumor progression and development. Upon drug treatment, some tumor cells can undergo a process of 'Redox Resetting' to acquire a new redox balance with higher levels of ROS accumulation and stronger antioxidant systems. Evidence has accumulated showing that the 'Redox Resetting' enables cancer cells to become resistant to anticancer drugs by multiple mechanisms, including increased rates of drug efflux, altered drug metabolism and drug targets, activated prosurvival pathways and inefficient induction of cell death. In this article, we provide insight into the role of 'Redox Resetting' on the emergence of drug resistance that may contribute to pharmacological modulation of resistance.

Keywords: cancer therapy; drug efflux; drug resistance; oxidative stress; redox modifications.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Antineoplastic Agents / pharmacology
  • Antioxidants / metabolism
  • Apoptosis
  • Autophagy
  • Cell Death
  • Cell Survival
  • Disease Progression
  • Drug Resistance, Neoplasm*
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Multidrug Resistance-Associated Proteins / metabolism
  • Neoplasm Proteins / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • Oxidation-Reduction*
  • Oxidative Stress
  • Protein Conformation
  • Reactive Oxygen Species / metabolism
  • Treatment Outcome

Substances

  • ABCB1 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Antineoplastic Agents
  • Antioxidants
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Reactive Oxygen Species
  • Fluorouracil
  • multidrug resistance-associated protein 1