Researchers identified a major weakness in lung cancer by blocking FSP1, a protein that protects tumors from ferroptosis. In mice, disabling FSP1 caused tumors to shrink dramatically. The study highlights a new strategy to treat lung cancers.
Researchers at NYU Langone Health have uncovered a powerful weakness in lung cancer by disabling a protein that helps tumors survive stress. Their latest findings show that when this protein—FSP1—is blocked, lung tumors in mice shrink dramatically as cancer cells trigger their own self-destruct mechanism.
The Hidden Role of Ferroptosis in Tumor Survival
The team focused on ferroptosis, a natural self-cleaning process that removes overly stressed or damaged cells. Although cancer cells should be vulnerable to this process, they often evolve tools to block it and continue growing. One of the key tools they use is FSP1, a protein that suppresses ferroptosis and shields tumors from oxidative stress.
The new study, published in Nature, revealed that shutting down FSP1 significantly weakens lung adenocarcinoma (LUAD), the most common type of lung cancer among non-smokers. When researchers genetically removed FSP1 from tumor cells in mice, the animals developed much smaller tumors. Blocking the same protein with an experimental drug, icFSP1, delivered similar results—up to 80% tumor reduction—and extended survival in treated mice.
Why FSP1 Is a Promising Drug Target
FSP1 works by preventing the buildup of reactive oxygen species (ROS), unstable molecules that can damage DNA, proteins, and cell membranes. In high amounts, ROS push cells into ferroptosis. By shutting down FSP1, the researchers forced cancer cells to face oxidative stress they could no longer escape.
The study also compared FSP1 with GPX4, another well-known ferroptosis-blocking protein. Results showed that FSP1 plays a much more decisive role in protecting lung cancer cells while having less importance in healthy cells. This may make FSP1-targeting drugs more effective and potentially safer.
Higher FSP1 levels were linked to worse survival among human lung adenocarcinoma patients, further strengthening its potential as a therapeutic target.
Looking Ahead: New Paths for Cancer Treatment
The research team plans to optimize FSP1 inhibitors and explore the approach in other aggressive cancers, including pancreatic tumors. Their work not only opens a new path for lung cancer treatment but also highlights ferroptosis as an underused tool in cancer therapy.