By Harshit
NEW YORK | NOVEMBER 24, 2025 | 1:40 AM EST
Lung cancer researchers at NYU Langone Health have uncovered a powerful new way to weaken lung tumors by exploiting a natural form of cell death known as ferroptosis — a highly inflammatory, iron-driven breakdown process that cancer cells typically work hard to avoid. A Nature study published on November 5 reveals that blocking a protein called FSP1 (ferroptosis suppressor protein 1) forces tumor cells into ferroptosis and shrinks lung adenocarcinoma tumors in mice by up to 80%.
The findings mark a major step forward in cancer biology by demonstrating, for the first time, that preventing cancer cells from escaping ferroptosis can dramatically reduce tumor burden, potentially offering a new strategy against the most fatal cancer worldwide.
Ferroptosis: The Cell Death Cancer Tries to Escape
Ferroptosis occurs when iron inside cells reacts with oxygen to generate reactive oxygen species (ROS) — highly unstable chemical molecules that damage DNA, proteins, and lipids. In healthy systems, ferroptosis functions as a selective cleanup process that removes dysfunctional or overly stressed cells.
Cancer cells, however, typically upregulate anti-ferroptosis defenses. By doing so, they prevent the buildup of toxic ROS and gain the ability to survive under metabolic stress, drug exposure, and immune attack.
One of the most important of these defenses is FSP1, a protein that neutralizes ROS and stabilizes cell membranes, giving tumor cells a major survival advantage.
Switching Off FSP1 Weakens Lung Adenocarcinoma
In the NYU Langone study, researchers genetically removed FSP1 from the tumor cells of mice engineered to develop lung adenocarcinoma (LUAD) — the most common lung cancer in non-smokers.
The results were striking:
- Tumors without FSP1 grew substantially slower
- Cancer cells showed intense oxidative damage
- Ferroptosis surged
- Tumor mass dropped by as much as 80%
To validate these findings, researchers then tested icFSP1, a next-generation experimental drug designed to block the FSP1 protein. Mice treated with icFSP1 experienced major tumor shrinkage and lived significantly longer.
“This first test of a drug that blocks ferroptosis suppression highlights the importance of the process to cancer cell survival and paves the way for a new treatment strategy,” said senior author Dr. Thales Papagiannakopoulos, associate professor of pathology at NYU Grossman School of Medicine.
Why FSP1 May Be Better Than Previous Targets
For years, scientists focused on another ferroptosis-related protein, GPX4, hoping to disable its protective effects in cancer. But GPX4 is essential to normal cell function — meaning that blocking it risks harming healthy tissue.
FSP1, by contrast:
- Is more active in lung cancer cells than in healthy cells
- Is linked with poor survival in human LUAD patients
- Offers a cleaner therapeutic target with potentially fewer side effects
This makes FSP1 one of the most promising ferroptosis-related drug targets discovered to date.
Reactive Molecules at the Center of Lung Tumor Vulnerability
At the heart of ferroptosis are reactive oxygen species, or ROS. These unstable molecules can:
- Attack cell membranes
- Damage DNA
- Trigger inflammatory cell death
Lung tumor cells constantly experience oxidative stress due to their fast growth and demanding metabolism — making them especially vulnerable. Blocking FSP1 removes a key layer of their protection, allowing ROS to accumulate until the cancer cells collapse.
Future Directions: Expanding the Therapy to Other Cancers
NYU researchers plan to:
- Optimize next-generation FSP1 inhibitors
- Test ferroptosis-based therapies in pancreatic cancer, which is highly resistant to conventional treatments
- Investigate why some tumors rely more heavily on ferroptosis suppression than others
- Explore combinations with immunotherapy
“We aim to translate these findings from the lab into novel clinical therapies for cancer patients,” said lead author Katherine Wu, an MD/PhD student in the Papagiannakopoulos lab.