The fastest growing cancer cells gorge themselves on a particular nutrient called glycine, a team of Boston-area scientists reported Thursday, providing a possible new lead in efforts to develop therapies that can stop a tumor’s rapacious growth.
Cancer has long been known to reprogram how cells burn energy, altering how they consume sugar. That nearly century-old observation has recently undergone a revival of interest, as it has become clear that genes that drive cancer also alter metabolism. Researchers are actively searching for therapies that could turn cancer cells’ distinctive appetites into a vulnerability, including scientists at Cambridge-based Agios Pharmaceuticals.
In the new study, published in the journal Science, researchers deployed a tool that could examine how cells take up and excrete more than 200 compounds and tried to find which were most associated with extremely fast growth. The team, led by Dr. Vamsi Mootha, a senior associate member of the Broad Institute and a systems biology professor at Harvard Medical School, analyzed the input and output of nutrients in 60 well-characterized cancer cell lines, populations of cells that can be grown in a dish. The compound that was most associated with rapid growth was unexpected—glycine, which is used to produce the building blocks of DNA and proteins.
Mootha said that the new technology is intended to provide more than a still photograph of a cell, which might give a misleadingly static view of what is transpiring; instead, the researchers wanted to gain real-time insight into the flow of compounds in and out of cells.
“The analogy I like to uses is the central arteries in the Boston highway system,” Mootha said. “If you take a single snaphsot, you’ll be able to quantify the number of pickup trucks and convertibles and sedans on the freeway system at a single moment. But you don’t know what their activities are; you don’t know if there’s a traffic jam or whether they are moving at 60 miles per hour. We are moving from snapshots to activity.”
Lewis Cantley, director of the cancer center at Beth Israel Deaconess Medical Center, and co-founder of Agios, said that the new result was somewhat surprising because much of the attention in the field had been focused on how cancer cells take up and utilize two other substances: glucose and glutamine. But he said the result reinforces two findings from last year, one from his own lab, which also showed that glycine metabolism appeared to be important to cancer cells.
To begin to test the validity of their result outside the laboratory dish, Mootha and colleagues explored the activity of genes involved in glycine metabolism in 1,300 breast cancer patients, and found that people with the most active genes were less likely to survive, showing that the nutrient is also associated with the disease in people.
Mootha added that much more work needs to be done to understand how glycine is used by cancer cells and whether intervening in its uptake and use could help slow the disease.
Dr. Ralph DeBerardinis, assistant professor of pediatrics and genetics at the University of Texas Southwestern Medical Center, said the finding provides a useful tool that can be more broadly applied, as well as immediate insights.
Today, physicians can use medical imaging techniques to measure tumors’ uptake of glucose. It might be interesting, DeBerardinis said, to develop a similar technique to monitor the uptake of glycine, since it was linked to rapid cell proliferation.
He also noted that one way of treating fast-growing pediatric leukemia is to use a drug that reduces the amount of an essential amino acid the cancer needs, essentially starving cancer cells. A similar strategy might be used to suppress glycine, he said, to see if doing so could stop tumor growth.