Blocking fatty acids slows prostate cancer progression
10 February, 2019
New research featuring in the journal Science Translational Medicine shows that fatty acids fuel prostate tumor growth. As blocking fatty acids seems to slow disease progression, fatty acid uptake may be a promising new therapeutic target for prostate cancer.
Renea Taylor, the deputy director of the Cancer Program at the Monash Biomedicine Discovery Institute in Clayton, Australia, and Prof. Matthew Watt, the head of the Physiology Department at the University of Melbourne, also in Australia, led the new research.
As Taylor, Prof. Watt, and their colleagues mention in their paper, even though prostate cancer grows slowly, preventing it from reaching an aggressive stage remains difficult.
The researchers wondered what it is that causes prostate tumors to become so aggressive. They wanted to determine what fuels the tumors and how prostate cancer metabolism differs from that of other cancers.
Taylor explains what pointed the researchers in the direction of fatty acids. "There is a strong link between obesity, diet, and poor outcomes in men who develop prostate cancer," she says.
"In particular, those men who consume more saturated fatty acids seem to have more aggressive cancer."
So, the scientists set out to examine more closely the role of fatty acids in prostate tumor growth.
Blocking fatty acid transport slows cancer
To do so, they took human tissue samples from people with prostate cancer and grafted them onto mice. They found that the uptake of fatty acids was higher in human prostate cancer and that these fatty acids fueled the tumor's biomass.
The researchers also noted that a fatty acid transporter called CD36 mediated these metabolic changes. Moreover, CD36 correlated with aggressive forms of prostate cancer.
Next, the researchers deleted the gene responsible for creating this transporter and examined the effects in the rodents with prostate cancer. Eliminating the gene decreased the signaling lipids that led to tumor formation and slowed down the progression of the cancer.
Furthermore, "CD36 antibody therapy reduced cancer severity in patient-derived xenografts," report the researchers, who go on to note that their results point to a new therapeutic target.
"These findings identify a critical role for CD36-mediated fatty acid uptake in prostate cancer and suggest that targeting fatty acid uptake might be an effective strategy for treating prostate cancer," the authors write.
Prof. Watt comments on the findings, saying, "We've known for many years that dysfunctional fatty acid metabolism is linked to many chronic diseases."
"Applying this knowledge to cancer and providing the evidence to develop a therapy to treat a disease that impacts so many men is deeply satisfying," he adds.
"Our whole concept is about giving more appropriate treatment earlier to stop men getting to the late or advanced stage. Our studies showed that blocking fatty acid transport is one way to do this."
Renea Taylor
According to the American Cancer Society, doctors will diagnose almost 175,000 people in the United States with prostate cancer in 2019, and more than 30,000 people will die as a result of this disease.
After lung cancer, prostate cancer is the "second leading cause of cancer death" in U.S. men.
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