How cutting lipids could starve breast cancer
Researchers at Huntsman Cancer Institute at the University of Utah (the U) have discovered that triple-negative breast cancer relies heavily on lipids for growth. These fatty acids, a defining feature of obesity, appear to drive tumor development. The study, funded by the National Cancer Institute and conducted using preclinical mouse models, indicates that breast cancer…
Researchers at Huntsman Cancer Institute at the University of Utah (the U) have discovered that triple-negative breast cancer relies heavily on lipids for growth. These fatty acids, a defining feature of obesity, appear to drive tumor development. The study, funded by the National Cancer Institute and conducted using preclinical mouse models, indicates that breast cancer patients and survivors with obesity might benefit from treatments that reduce lipid levels, and that high-fat diets such as the ketogenic diet could be harmful for them.
“The key here is that people have underestimated the importance of fats and lipids in the all-encompassing term that is obesity,” says Keren Hilgendorf, PhD, a Huntsman Cancer Institute investigator and assistant professor of biochemistry at the U. “But our study shows that breast cancer cells are really addicted to lipids, and the abundance of lipids in patients with obesity is one of the reasons that breast cancer is more prevalent and more aggressive in these patients.”
High lipid levels in the blood, a condition known as hyperlipidemia, often accompany obesity. Hilgendorf and her colleagues, Amandine Chaix, PhD, assistant professor of nutrition and integrative physiology, and Greg Ducker, PhD, assistant professor of biochemistry, studied mice fed high-fat diets and others genetically designed to have hyperlipidemia without other hallmarks of obesity, such as elevated glucose and insulin. In both cases, excess lipids alone were enough to speed up tumor growth.
“The idea is that lipids, which form the surface membrane of the cell, are like building blocks,” says Chaix. “If a cell receives the signal to proliferate and more building blocks are available, the tumor is going to grow more easily. We see that a high amount of lipids enables this proliferation.”
When researchers reduced lipid levels in the mouse models, tumor growth slowed, even in the presence of high glucose and insulin. While mice and humans have different metabolisms, these findings may point to new therapeutic approaches or diet recommendations to help control cancer growth.
“We think this has therapeutic implications, because if you could just lower the lipids — which we already know how to do in patients, for example, with lipid-lowering medication — that could be a way to decelerate breast cancer growth. If we can target these high levels of fat in the blood, the cancer suffers because the lipids are no longer feeding the cancer,” says Hilgendorf. “But while our results in mice were striking, there are clear limitations in directly projecting these findings onto human patients. More research using human samples and patients will be necessary to confirm our hypotheses.”
The results may also influence how patients and survivors with obesity manage their weight. Doctors often encourage weight loss to help lower the risk of cancer returning or spreading, but there is limited evidence about which diets are safest or most effective.
Many patients consider the keto diet, which emphasizes high fat and very low carbohydrate intake to trigger a metabolic state called ketosis, where the body burns fat instead of carbs for energy.
The research team cautions that while such diets can promote weight loss, patients should carefully assess their overall metabolic health before adopting them.
“For patients who are diagnosed with breast cancer and have an elevated BMI, we would advise them to consult their physician and develop a weight loss plan as part of their treatment. If you have high cholesterol levels to start with, think about a weight loss plan or potential pharmaceuticals that could lower your lipid levels,” says Ducker. “As our study shows, diets like keto that are very high in fat can have serious unintended side effects — even causing the tumor to grow.”
The study suggests that lipids may also fuel tumor growth in patients with obesity who have other types of breast cancer, or ovarian or colorectal cancers. The research team says the next steps will be to preclinically evaluate how anti-lipid drugs could improve responses to chemotherapy. They also want to better understand how the lipids are feeding cancer cells.
Chaix, Ducker, and Hilgendorf also stress that their study is one specific type of cancer adapting to an obese environment, and that the keto diet may be beneficial for other types of cancer.
The results of the study were published in Cancer & Metabolism. Renan Vieira, doctoral student at the U, is the first author. The critical research happening every day at Huntsman Cancer Institute is supported by the National Institutes of Health/National Cancer Institute, including cancer center support grant P30 CA042014, U01 CA272529-03S1, NCI UH2 CA286584, as well as Huntsman Cancer Foundation.