Asparagine encourages metastatic triple-negative breast cancer, study suggests

Diet and disease, two words that aren’t associated with one another maybe as often as they should. However, a recent multicentre study published in Nature suggests that a single amino acid commonly found in various foods may hold the key to preventing the spread of triple-negative breast cancer.

Triple-negative breast cancer is one of the more aggressive forms of the disease, however, due to its heterogeneity, prognoses can vary widely. Triple-negative refers to the lack of oestrogen, progesterone and human epidermal growth factor receptor 2 (HER2) receptors which are common targets for cancer treatments, such as hormone therapies that target the oestrogen and progesterone receptors, and targeted treatments like trastuzumab for HER2 positive disease. This limits the treatment options available, with chemotherapy, radiotherapy and surgery being the most effective.

The researchers, spread over more than a dozen centres worldwide, investigated the amino acid asparagine which is found in foods such as asparagus, beef, dairy and nuts. Previous research has shown that a subset of cells detaches from the primary tumour, colonising other areas of the body, causing metastasis.

The team studied these subsets of cells in mice to ascertain if there was a measurable relationship between certain cell characteristics and their ability to form secondary tumours. They found that cells with higher levels of asparagine synthase were more able to colonise other parts of the body, leading to a greater chance of metastatic relapse. When asparagine levels were controlled, either through dietary restrictions, the use of L-asparaginase, or a reduction in asparagine synthase, the metastatic potential of the tumour was reduced, improving outcomes. Likewise, if bioavailable asparagine levels were elevated through increased dietary asparagine or asparagine synthase expression, the tumour had greater metastatic potential.

  

The study results are extremely suggestive that changes in diet might impact both how an individual responds to primary therapy and their chances of lethal disease spreading later in life."

The study's senior author, Gregory J. Hannon, PhD, professor of Cancer Molecular Biology and director, Cancer Research UK Cambridge Institute, University of Cambridge.

The researchers hope that early-phase human trials can now take place, where the patients would eat a low-asparagine diet. If this resulted in reduced asparagine levels then it would progress to a full-scale trial where patients would employ the low-asparagine diet, alongside conventional chemotherapy and immunotherapy regimens, with the hope that their findings could be applied to other cancers.

 

 

This study may have implications not only for breast cancer, but for many metastatic cancers."

Ravi Thadhani, MD, MPH, vice dean, Research and Graduate Research Education, at Cedars-Sinai.

 

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