Scientists find a new drug to treat pancreatic cancer

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In a new study, researchers found that a compound in development for a rare kidney stone disease may have the potential to fight against pancreatic cancer.

The compound starves tumors of amino acid, cysteine, which was found to be critical to the survival of pancreatic cancer cells.

The research was conducted by a team from Columbia University.

Pancreatic cancer is a uniquely lethal disease, with an average survival rate of just six months after diagnosis. Doctors are in desperate need of new treatments.

Most pancreatic tumors ramp up the production of oxidants that can kill many normal cells. Yet, pancreatic tumors thrive under these toxic conditions by importing large amounts of cysteine into their cells.

All cells, including pancreatic tumor cells, use cysteine to manufacture molecules that detoxify oxidants.

Since pancreatic tumors appear to depend on cysteine import for their survival, the team hypothesized that it might be possible to slow tumor growth by selectively targeting this amino acid.

That strategy of starving the pancreatic cancer cells of cysteine worked.

When the gene that controls cysteine import was knocked out in mice with pancreatic cancer closely resembling human tumors, cutting off cancer’s supply of cysteine, the tumors stopped growing and median survival time doubled.

The researchers achieved similar results when the mice were treated with cysteinase—an experimental drug that breaks down cysteine in blood.

(Cysteinase is currently being developed by researchers at the University of Texas Southwestern Medical Center for the treatment of cystinuria, a rare genetic disorder in which high levels of cysteine concentrate in the urine, causing kidney and urinary tract stones.)

Human pancreatic cancer cells also appear to be dependent on cysteine, the researchers found. When cysteinase was added to human pancreatic cancer cells in tissue culture, cancer cells died.

According to the team, when starved of cysteine, the pancreatic cancer cells are killed by a process called ferroptosis, the researchers also found.

Ferroptosis is a form of programmed cell death that results from oxidation damage to cell membranes.

The drug ferroptosis may also be harnessed against other types of cancer.

One of the most exciting aspects of the new study is that cysteine depletion did not appear to harm healthy, normal cells.

The team currently is exploring the detailed cellular and molecular mechanisms of ferroptosis in pancreatic cancer, in the hope that this understanding might lead to additional therapeutic approaches.

One author of the study is Kenneth P. Olive, Ph.D., an associate professor of medicine.

The study is published in Science.

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