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Langone Study Finds New Method of Killing Lung Cancer Cells

Researchers+from+Perlmutter+Cancer+Center+at+NYU+Langone+Health+Center+have+published+a+paper+providing+evidence+for+a+new+method+of+killing+lung+cancer+cells.+%0A
Researchers from Perlmutter Cancer Center at NYU Langone Health Center have published a paper providing evidence for a new method of killing lung cancer cells.

Researchers from Perlmutter Cancer Center at NYU Langone Health Center have published a paper providing evidence for a new method of killing lung cancer cells.

Photo by Lily Xing

Photo by Lily Xing

Researchers from Perlmutter Cancer Center at NYU Langone Health Center have published a paper providing evidence for a new method of killing lung cancer cells.

By Christine Lee, Staff Writer

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Researchers from the Perlmutter Cancer Center at NYU Langone Health published a paper providing evidence for a new method of killing lung cancer cells in the Nov. 22 edition of Nature magazine, according to Langone’s website.

Richard Possemato, an assistant professor at the Department of Pathology and lead author of the study, published the research information with the help of fourth year Medical Center student Vladislav Svidersky.

“We are interested in understanding how changes in the environment of a cancer [in vitro culture or tumor] affected the metabolic pathways that cells needed to survive,” Possemato said, discussing the motivations behind conducting the study. “Therefore, we undertook a genetic screen in cancer cells growing in traditional cell culture conditions or as tumor xenografts in the mouse mammary fat pad, which meant to simulate the environment of a mammary tumor.”

The team focused on three elements within human cells: iron, sulfur and oxygen, as well as an enzyme called NFS1. Enzymes are catalysts within a human body structured to accelerate chemical reactions.

NFS1 groups iron and sulfur together into iron-sulfur clusters, which help fight lung cancer in a myriad of ways. Iron-sulfur clusters are sensitive to oxygen, so if an environment has high levels of oxygen, these clusters get destroyed, making it necessary for NFS1 to create more clusters. Cancer cells in the lungs depend on NFS1 to create more iron-sulfur clusters.

One of the study’s more prominent findings came when the team treated lung cells with pro-oxidants, making the cells produce less functional NFS1. This suggested that after suppressing the enzyme, the surrounding oxygen would be able to break down the iron-sulfur clusters created by NFS1.

“This is the first description of iron-sulfur cluster biosynthesis as a pathway that is altered in cancer, and the first description of a metabolic pathway whose dependence is related to the concentration of an extracellular metabolite,” Possemato said. “Moreover, suppression of NFS1 or activation of the downstream iron-starvation response provides an avenue to induce ferroptosis in cancer.”

According to Possemato, the study’s results have direct implications within the field, and can be used to produce more effective medications.

“There is a growing body of literature suggesting that proper management of reactive oxygen species is an important adaptation in cancer, particularly lung adenocarcinoma,” Possemato said. “However, there are currently no drugs that readily target this liability. Hopefully this and similar work will spark the production of such drugs, which would provide a unique weapon in the armamentarium of anticancer treatments.”

Possemato said that in the future, the team would like to develop an inhibition of the NFS1, since it should be readily druggable as a metabolic enzyme. The team additionally seeks to understand how the NFS1 suppression affects tumor development in genetic mouse models.

A version of this article appeared in the Monday, Dec. 4 print edition. Email Christine Lee at [email protected]

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