A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers

Targeting ferroptosis, a unique cell death modality triggered by unrestricted lipid peroxidation, in cancer therapy is hindered by our incomplete understanding of ferroptosis mechanisms under specific cancer genetic contexts. KEAP1 (kelch-like ECH associated protein 1) is frequently mutated or inactivated in lung cancers, and KEAP1 mutant lung cancers are refractory to most therapies, including radiotherapy. In this study, we identify ferroptosis suppressor protein 1 (FSP1, also known as AIFM2) as a transcriptional target of nuclear factor erythroid 2-related factor 2 (NRF2) and reveal that the ubiquinone (CoQ)-FSP1 axis mediates ferroptosis- and radiation- resistance in KEAP1 deficient lung cancer cells. We…

• CP
  Cancer Prevention and Research Institute of Texas

  Awards: RP170067, P30CA016672, RP220258
• UO
  University of Texas Health Science Center at Houston
• NI
  National Institutes of Health

  Awards: P30CA016672, R01CA247992, R01CA181196, RP220258, R01CA244144
• UO
  University of Texas MD Anderson Cancer Center

  Awards: RP170067, P30CA016672