Researchers at NYU Langone Health report that inhibiting the protein FSP1 induces ferroptosis and markedly slows lung adenocarcinoma in mouse models. The study, published online in Nature on November 5, 2025, found tumor growth reductions of up to 80% in preclinical tests, according to the institution.
Lung cancer is the leading cause of cancer deaths worldwide, with recent global estimates attributing roughly 1.8 million deaths per year to the disease. Adenocarcinoma is the most common subtype of lung cancer and the predominant form seen in people who have never smoked; it accounts for about 40–45% of lung cancer cases in the United States.
The new Nature study examined ferroptosis—a form of cell death driven by uncontrolled lipid peroxidation—and how lung tumors evade it. Using genetically engineered mouse models of KRAS-driven lung adenocarcinoma, the team showed that knocking out ferroptosis suppressor protein 1 (FSP1, also known as AIFM2) increased lipid peroxidation and robustly restricted tumorigenesis. The authors also probed glutathione peroxidase 4 (GPX4), another key ferroptosis suppressor, and confirmed that pharmacologic inhibition of FSP1 provided therapeutic benefit in multiple preclinical models.
According to an NYU Langone news release accompanying the paper, treatment with a next-generation FSP1 inhibitor, icFSP1, reduced tumor growth by as much as 80% and extended survival in mice—results comparable to tumors engineered to lack the FSP1 gene. The release framed the work as an early test that pharmacologically blocks ferroptosis suppression in vivo.
Senior author Thales Papagiannakopoulos of NYU Grossman School of Medicine said the findings suggest that disabling cancer cells’ ferroptosis defense could open a new treatment avenue for lung cancer. Lead author Katherine Wu added that the group aims to optimize FSP1 inhibitors and explore ferroptosis-based strategies in other solid tumors, including pancreatic cancer.
The study further reports that elevated FSP1 expression correlates with worse outcomes in patients with lung adenocarcinoma, while GPX4 expression showed weaker prognostic value. Because FSP1 appears to play a larger role in ferroptosis protection within tumors and a smaller role in normal cell function, the authors note it could be a more tractable therapeutic target than GPX4, potentially with fewer side effects.
The research involved collaborators from NYU Langone, Seoul National University, UCLA, Helmholtz Munich, and UC San Diego. Funding included grants from the U.S. National Institutes of Health, the American Cancer Society, the Deutsche Forschungsgemeinschaft, the European Research Council, and NYU’s Perlmutter Cancer Center.
References: Nature (published November 5, 2025); institutional announcements from NYU Langone Health for additional detail on preclinical efficacy.
