New Drug Strategy Forces Lung Cancer Cells Into Self-Destruction

Researchers at NYU Langone Health have identified a promising new therapeutic approach that triggers the self-destruction of lung cancer cells by disabling a key protein that helps tumors survive harmful cellular stress.

Published November 5 in Nature, the study shows that blocking a protein known as ferroptosis suppressor protein 1 (FSP1) significantly reduced tumor growth - by up to 80 percent—in mice with lung adenocarcinoma (LUAD), the most common form of lung cancer in nonsmokers and a leading cause of global cancer deaths.

The findings center on ferroptosis, a natural form of cell death caused by the toxic buildup of reactive oxygen molecules. While this process normally eliminates damaged cells, cancer cells often evolve mechanisms that prevent ferroptosis, enabling them to continue growing uncontrollably.

“This is the first demonstration that blocking a cancer cell’s ability to suppress ferroptosis can dramatically slow tumor progression,” said senior author Thales Y. Papagiannakopoulos, PhD, associate professor of pathology at NYU Grossman School of Medicine. “It marks a significant step toward a new class of therapies.”

Using genetically engineered mice, researchers showed that deleting the FSP1 gene or inhibiting the protein using a drug candidate called icFSP1 both increased cancer cell death and improved survival. The study also found that FSP1 may be a more precise drug target than the long-studied GPX4 protein, with potentially fewer side effects.

Lead author Katherine Wu, an MD/PhD student, noted that future work will focus on optimizing FSP1 inhibitors and investigating whether ferroptosis-based therapies could help treat other solid tumors such as pancreatic cancer.

The research was conducted in collaboration with scientists from Seoul National University, UCLA, Helmholtz Munich, and UC San Diego, and was supported by grants from the National Institutes of Health, the American Cancer Society, and international funding organizations.

Source: NYU Langone Health / NYU Grossman School of Medicine
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