Kidney stone drug found to starve pancreatic cancer cells to death
Like all cells in the body, cancerous cells need nutrients and energy to survive, which presents researchers with an opportunity to cut off the supply and slow their spread. A research team at Columbia University has made an exciting discovery in this area, finding that a compound currently under development for a rare kidney stone disease can starve pancreatic cancer cells of a key amino acid they depend on, a technique that proved to stop tumor growth in mice.
“We’re very encouraged by these results,” says Kenneth P. Olive, PhD, senior author of the study. “Pancreatic cancer is a uniquely lethal disease, with an average survival rate of just six months after diagnosis. We’re in desperate need of new treatments.”
One of the ways pancreatic cancer causes harm is by driving the production of oxidants, which can be fatal to healthy cells in the body but leave the tumor cells intact. The reason for this is an amino acid called cysteine, which the tumor cells import in huge quantities and allows them to produce molecules that neutralize the toxic effect of the oxidants.
“Since pancreatic tumors appear to depend on cysteine import for their survival, we hypothesized that it might be possible to slow tumor growth by selectively targeting this amino acid,” Olive says.
The team worked with mouse models of pancreatic cancer closely resembling tumors in humans. They engineered the mice to be missing the gene that controls cysteine import and found that this missing piece led to a halt in the tumors growing and a doubling of the median survival time.
In another experiment, the team treated the mice with a drug called cysteinase, with similar results. This compound is under development for the treatment of a rare genetic disorder called cystinuria, in which high amounts of cysteine build up and lead to the formation of kidney and urinary tract stones. The scientists also added cysteinase to tissue culture containing human pancreatic cancer cells, causing those cells to die.
The team is now working to see if the drug's effectiveness can be ramped up by combining it with other cancer treatments, such as immunotherapy. One of the promising outcomes of this approach, the team notes, is that it appears to leave normal cells unharmed.
“You might imagine that all the cells of your body need every amino acid equally, but we knew from prior studies that most normal cells need only very low levels of cysteine,” Olive says. “Our whole goal in targeting this difference between normal cells and cancer cells is to develop a treatment that is toxic to cancer and gentle on the rest of the body.”
The research was published in the journal Science.
Source: Columbia University