Scientists have discovered that an amino acid called asparagine is essential for breast cancer spread, and by restricting it, cancer cells stopped invading other parts of the body in mouse models, according to research published in the journal Nature.
Most breast cancer patients do not die from their primary tumour, but instead from metastasis, or the spread of cancer to the lungs, brain, bones, or other organs. To be able to spread, cancer cells first need to leave the original primary tumor, survive in the blood as “circulating tumor cells,” and then colonize other organs.
By finding a mechanism to block metastasis, researchers hope to save lives.
UNC Lineberger researchers were part of the study, which was led out of the Cancer Research UK Cambridge Institute. They found that blocking the production of asparagine with a drug called L-asparaginase in mice with aggressive triple negative breast tumors, and putting them on a low-asparagine diet, greatly reduced the breast tumor’s ability to spread.
Asparagine is an amino acid – the building blocks that cells use to make proteins. While the body can make asparagine, it’s also found in our diet, with higher concentrations in some foods including, asparagus.
Researchers were prompted by these mouse studies to examine data from breast cancer patients. These data indicated that the greater the ability of breast cancer cells to make asparagine, the more likely the tumor was to spread. In several other cancer types, increased ability of tumor cells to make asparagine was also found to be associated with reduced survival.
“We don’t yet know how broadly applicable this is to cancer patients; we’re going to figure that out,” said UNC Lineberger’s Charles M. Perou, PhD, the May Goldman Shaw Distinguished Professor in Molecular Oncology, and a professor of genetics and of pathology and laboratory medicine. “It does highlight, again, the importance of cancer metabolism, and suggest that it may be an area of therapeutic intervention in the future. It’s not ready for clinical action today, but it’s a promising approach. We and many others are pursuing this cancer metabolism angle.”
UNC Lineberger’s Lisa A. Carey, MD, physician-in-chief of the N.C. Cancer Hospital, and the Richardson and Marilyn Jacobs Preyer Distinguished Professor, and co-author of the paper, offered a word of caution that more research needs to be done to evaluate diet restriction in cancer patients to restrict metastasis.
“We can potentially manage cancers better in the future if we really understand what nutrients they require,” said Carey.
Carey added that there is a drug used to treat leukemia that uses asparagine-based metabolism as its target.
“It’s important for us to understand how cancers grow, and how they feed themselves, and what they require in order to grow,” Carey said. “That may be something they can modulate.”
The study was supported by The Hope Funds For Cancer Research, Human Frontier Science Program, Susan G. Komen Foundation, NCI Breast SPORE program, Breast Cancer Research Foundation, Triple Negative Breast Cancer Foundation, NIH, The Institute of Cancer Research, CRUK Grand Challenge Award, Cancer Research UK, and the DOD BCRP.
University of North Carolina at Chapel Hill School of Medicine