A new approach in the treatment of aggressive breast cancer might require dietary changes to reduce the levels of one amino acid, which can be derived from asparagus, among other foods.
Triple-negative breast cancer is one of the most aggressive forms of breast cancer, and it is able to spread quickly.
It is typically resistant to traditional forms of treatment, such as chemotherapy and radiotherapy.
New research conducted by several institutions, including the Cancer Research UK Cambridge Institute in the United Kingdom, has sought to uncover some of the reasons why this type of cancer not only survives but also thrives in the body, hoping that this will eventually lead to improved therapeutic approaches.
In the study, whose findings are now published in the journal Nature, lead study authors Profs. Greg Hannon and Simon Knott and their team reported that an important nutrient that facilitates the spread of this type of breast cancer is asparagine.
Asparagine is a non-essential amino acid often synthesized by our bodies from some of the dietary products that we consume. The current study investigated whether or not limiting the levels of asparagine in the body could help to slow down tumor growth.
“Our study adds to a growing body of evidence that suggests diet can influence the course of the disease,” says Prof. Knott.
Tumors thrive on asparagine
The researchers investigated the relationship between asparagine and breast cancer metastasis, or tumor spread, in a mouse model of triple-negative breast cancer.
Prof. Hannon and team had a two-pronged approach. On the one hand, they administered the mice L-asparaginase, which is chemotherapy drug currently used in the treatment of acute lymphoblastic leukemia, which is known to thrive on asparagine. L-asparaginase acts by inhibiting the production of the amino acid asparagine in the body.
On the other hand, the scientists also restricted the mice’s diets, so that they would have a lower asparagine content. This double approach resulted in a reduction of breast cancer tumor metastases in the mice.
“Our work has pinpointed one of the key mechanisms that promotes the ability of breast cancer cells to spread,” says Prof. Hannon.
“When the availability of asparagine was reduced, we saw little impact on the primary tumor in the breast, but tumor cells had reduced capacity for metastases in other parts of the body.”
Prof. Greg Hannon
In contrast, when the researchers fed the animals foods that had a high content of asparagine, the tumors spread more rapidly.
Additionally, to confirm the role played by asparagine in the spread of cancerous tumors, the team analyzed data from breast cancer patients.
They found that there was a positive correlation between the cancer cells’ ability to synthesize asparagine and the tumors’ chance of spreading to other sites in the body.
Even more worryingly, the cancer cells’ ability to produce this amino acid was also linked with a lower rate of survival among the patients.
“This finding adds vital information to our understanding of how we can stop cancer spreading — the main reason patients die from their disease,” notes Prof. Hannon.
‘Changes in diet might impact therapy’
As their next step, the researchers are interested in setting up an early-phase clinical trial that would allow them to understand how diet affects the levels of asparagine in the body.
For this purpose, Prof. Hannon and team propose to recruit a group of healthy participants, who would then agree to follow a diet low in asparagine.
“The [new study’s] 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,” says Prof. Hannon.
Should this experiment succeed in reducing asparagine levels in the participants’ bodies, then the researchers would go ahead and recruit participants with a cancer diagnosis for the next phase of their clinical trials.
At this point, adds Prof. Knott, the study participants would probably also receive chemotherapy and immunotherapy, so that the diet and treatments may boost each other’s effect.
The researchers think that their results so far suggest that an asparagine-reducing therapy may be applicable not only to triple-negative breast cancer but also to other cancer types, citing kidney, head, and neck cancers as potential targets in the future.