The interplay of oncogenic signaling, oxidative stress and ferroptosis in cancer

Int J Cancer. 2023 Sep 1;153(5):918-931. doi: 10.1002/ijc.34486. Epub 2023 Mar 7.

Abstract

Oncogene-induced hyper-proliferation in cancer cells is accompanied by the onset of different stresses, including DNA-replication stress, metabolic stress and oxidative stress. Excessive accumulation of reactive oxygen species (ROS) plays a pivotal and contradictory role in tumor progression. ROS dictates a multitude of cell signaling pathways to facilitate the malignant transformation of tumor cells. In the meantime, oxidative burden in tumor cells mandates reinforcing antioxidant capacity to mitigate detrimental damages. The addiction to oxidative stress and increased iron demands in cancer cells also impinges on the sensitivity of ferroptosis. Targeting redox homeostasis and ferroptosis to overcome drug resistance in cancer treatment has become an attractive research topic. However, the roles of oncogenic signaling in redox regulation and ferroptosis have not been comprehensively discussed. In this review, we summarize current knowledge regarding the interplay between redox regulation and ferroptosis in the context of cancer biology. We emphasize the implication of oncogenic signaling in redox homeostasis and ferroptosis regulation. We also provide an overview of strategies targeting oxidative stress and ferroptosis in cancer treatment.

Keywords: cancer; ferroptosis; oncogneic signaling; oxidative stress; redox homeostasis.

Publication types

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

MeSH terms

  • Ferroptosis*
  • Humans
  • Neoplasms* / pathology
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • Reactive Oxygen Species