Hot Topic: Manipulating Cell Metabolism to Attack Cancer

Many of us associate the word “metabolism” with the ability to burn calories as our cells convert what we eat to energy. 

Cancer cells have their own shrewd metabolism, allowing them to reproduce very quickly— a hot area of research enabling scientists to search for ways to manipulate cancer-cell metabolism to stop or slow the disease.

“Every tissue or cell type in the body has different metabolic needs but as cells become cancerous their metabolism shifts in ways that are very different from normal cells,” says Josh Munger, Ph.D., associate professor of Biochemistry and Biophysics at Wilmot. “Being able to identify those differences is critical for developing treatment targets.”

He and Hucky Land, Ph.D., the Robert and Dorothy Markin Professor and director of research at the Wilmot Cancer Institute, recently pinpointed a key source of the problem with cancer-cell metabolism. Their work was published by the journal Cell Reports.

In a close collaboration between their labs, they showed for the first time that cancer-causing mutations control and alter the way cancer cells biosynthesize and replicate.  

It’s been known for decades that cancer cells siphon glucose from the bloodstream at alarming rates. But cancer’s sugar addiction is only one part of the story, Land explains.

Sugar is metabolized differently by cancer cells. They switch from burning to fermenting sugar, a process that’s fueled by cancer-causing mutations, the Land and Munger labs discovered. Wilmot researchers also found that in cancer cells, sugar fermentation facilitates the consumption of glutamine, another nutrient source. Glutamine is abundantly available in the bloodstream, and cancer cells devour it to support cell division.

“Our paper demonstrates that cancer cells, but not normal cells, depend on this link between sugar fermentation and glutamine consumption,” Land says. “This suggests a novel way that we might be able to intervene with treatment.”

Bradley Smith, Ph.D., a scientific staff member in the Land lab, led the laboratory experiments conducted with colon cancer cells. Early data show that by blocking enzymes that are specific to colon cancer cell metabolism, tumor growth can be slowed or stopped.  Elsewhere, scientists are studying the metabolism of pancreatic cancer cells and other cancers.

Next, Land says, researchers want to learn whether the metabolism of cancer cells changes and adapts as the disease spreads, and if different cancers have different metabolic actions.

“How can we break disease recurrences by manipulating metabolism?” Land raises the question, noting that the answer may not be far off. When Wilmot published its important discovery in October, three other worldwide science labs weren’t far behind with their own intriguing new data on cancer cell metabolism.  

“There’s a huge interest in this topic,” he says. “We’re at a crucial point in truly understanding cancer-cell metabolism and how we can exploit it for treatment.”