Ferroptosis sensitivity as a vulnerability for the development and treatment of non-small cell lung cancer

• Applicant: Dr. Irina Ingold
• Subject Area: Hematology, Oncology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 449499544

Ferroptosis is a novel type of regulated, non-apoptotic cell death, which was initially described in 2012 and is characterized by an uncontrolled, iron-dependent accumulation of lipid peroxides in the cell membrane. Ferroptotic cell death is associated with various pathological conditions such as neurodegenerative diseases including amyothrophic lateral sclerosis (ALS), multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and stroke as well as ischemia/reperfusion injury (IRI). Since ferroptosis was initially described in RAS mutated tumor cells, it quickly emerged as a potential therapeutic strategy to eradicate cancer cells. Meanwhile it has become evident that ferroptosis execution is not restricted to tumors carrying mutated RAS, and that especially therapy-resistant and dedifferentiating cancer cells acquire a marked vulnerability to ferroptosis. Despite intense research performed within the last years to study ferroptosis in the context of cancer, still little is known about the role of the key ferroptosis players in tumor initiation and progression. The goal of this project is to study the impact of the main ferroptosis regulators for tumorigenesis and progression by using transgenic mouse models in the context of non-small cell lung cancer, a type of cancer with the highest incidence and highest mortality rate worldwide, due to relapse and regression of the tumor. The investigation of this question is of utmost importance and can be used in a clinical context to design novel treatment strategies based on ferroptosis induction.

• DFG Programme: Research Grants