The mechanisms and therapeutic targets of ferroptosis in cancer

Long Ye, Fengyan Jin, Shaji K. Kumar, Yun Dai

Research output: Contribution to journalReview articlepeer-review


Introduction: Ferroptosis, a form of programmed cell death, is mediated primarily by lipid peroxidation via a unique iron-dependent process. The mechanisms of ferroptosis involve the metabolisms of amino acids, irons, and lipids, and the regulation of antioxidant systems. Evidence supports the roles of ferroptosis in cancer, while metabolic reprogramming (a hallmark of cancer) renders tumor cells highly vulnerable to ferroptosis and thus provides a rationale for ferroptosis-targeted therapy for cancer. Area covered: This article examines the current understanding of the mechanisms and related signaling pathways involving ferroptosis; it focuses on novel targets in cancer and its treatment and drug resistance. The development of ferroptosis-targeted therapy, especially in combination with conventional or non-conventional therapies, are considered with dilemmas and key questions in this research area. Expert opinion: An increasing number of potential targets and ferroptosis inducers (FINs) have been identified to treat cancer. However, no specific FIN has entered clinical trials thus far, likely due to poor efficacy and high toxicity in vivo. Thus, new FINs with high selectivity and bioavailability are required to target tumor cells more specifically and potently. Particularly, the combination of FINs with chemotherapy, radiotherapy, targeted therapy, and immunotherapy warrants clinical investigation in the future.

Original languageEnglish (US)
Pages (from-to)965-986
Number of pages22
JournalExpert opinion on therapeutic targets
Issue number11
StatePublished - 2021


  • Auranofin
  • Cancer
  • altretamine
  • cisplatin
  • combination therapy
  • drug resistance
  • ferroptosis
  • fubendazole
  • itraconazole
  • ivosidenib
  • lapatinib
  • metabolic reprogramming
  • methotrexat
  • mitochondrial dysregulation
  • pioglitazone
  • programmed cell death
  • rosiglitazone
  • sorafenib
  • statins
  • sulfasalazine
  • therapeutic target
  • troglitazone
  • zileuton

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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