Half of all cancer patients suffer from a wasting syndrome called cachexia. Affected patients lose weight, including muscle, no matter how much they eat. The wasting is the immediate cause of about a third of all cancer deaths.
Those stark numbers have spurred research into what exactly causes cachexia in patients with cancer and how it might be avoided. Until recently, doctors thought cancer-associated cachexia was a sign of an energy-hungry tumor taking food from healthy cells. That view doesn’t account for the fact that small tumors can also cause wasting.
Researchers increasingly suggest that the “brown fat” that has been studied as an antidote to obesity could also trigger wasting in patients with cancer.
Brown fat, which looks browner than conventional fat under a microscope, is a tool for the body to stay warm: Newborns have more of it than adults. Rather than simply storing calories, brown fat burns them.
In overweight patients, converting white fat to brown would be helpful. But for patients with cancer, it’s a life-threatening problem that leads them to become frail and less able to withstand their treatments or fight off otherwise minor illnesses.
Slowing Fat 'Browning' to Prevent Cachexia
In a study conducted at the Spanish National Cancer Research Centre in Madrid, researchers Michele Petruzzelli and Erwin Wagner tracked mice infected with different types of cancer and found that white fat converted into brown fat in all the types of cancer well before the animals showed any signs of wasting.
What, then, might doctors do to prevent patients from experiencing cachexia and what effect that might have on the progression of cancer?
“It is impossible at the moment to predict what would happen if we were able to prevent cachexia. Would cancer behave like a chronic disease and spare (many) years of life? We definitely hope so,” Petruzzelli said in an email.
Because cachexia is linked to inflammation, Petruzzelli and Wagner used a drug similar to a beta-blocker to stop one promoter of inflammation, interleukin-6, in the cancerous mice. Reducing inflammation slowed the rate at which white fat turned into brown fat, they reported in Cell Metabolism.
There are no approved drugs that prevent the conversion of white fat into brown, though some are being studied. There aren't any drugs that can trigger the conversion as a fix for obesity either.
Researchers Look for Other Possible Causes of Wasting
In a separate study, researchers at the Dana-Farber Cancer Institute in Boston neutralized a chemical secreted by cancer tumors themselves. Neutralizing parathyroid hormone-related protein, or PTHrP, from the tumor slowed the shift from white fat to brown fat in mice with cancer, the researchers reported in Nature. It also stopped the loss of muscle mass.
But PTHrP “is definitely not the whole answer,” lead author Bruce Spiegelman said in a press statement. It may drive cachexia in some patients but not in others.
The two studies point in the same direction for further research. They indicate that if researchers can identify which biomarkers suggest that a patient is at higher risk of cachexia, like interleukin-6 or PTHrP, doctors could act sooner to prevent it.
Researchers will also have to continue looking for ways to slow the conversion of white fat into brown before Petruzzelli’s dreams of cancer as a chronic illness can be realized.