Arginine Starvation Could Help Fight Cancer, Study Finds

What arginine deficiency can do to cancer cells?

Recent research published in Science Advances reveals that arginine, an amino acid naturally produced by our bodies and found in foods like fish, meat, and nuts, is an essential nutrient for cancer cells. The researchers, from Sohail Tavazoie’s Laboratory of Systems Cancer Biology at Rockefeller University, found that in various human cancers, arginine becomes limited, causing the cancer cells to manipulate proteins to more efficiently take up arginine and other amino acids. In a bid to continue growing, they induce mutations that reduce their reliance on arginine.

The researchers discovered this connection as part of a larger study on codons, triplets of DNA bases that each contain the recipe for producing a single amino acid. In combing through the Cancer Genome Atlas, they documented thousands of instances of codon mutations, but one stood out among all cancers: arginine codons, which were lost during mutations far more than they should have been.

To investigate the impact of arginine deficiency, the researchers grew cancer cells in the lab and starved them of arginine. The cancer cells began mutating as they tried different ways to secure access to a renewed supply of the dietary essential. One successful method was to increase the amount of amino acid transporter proteins so that the cells could more efficiently take up arginine and other amino acids. But even these functional knockoffs tended to be meager sources, and the errors compounded as the cells replicated, resulting in changes to the genome such as mutated genes and misshapen proteins.

Interestingly, this ability of the cancer cells to manipulate codons to their bidding could potentially lead to their undoing. In the process of trying to survive while malnourished, the cells accumulate so many mutations that they may begin to look very strange to the immune system. Once deeply mutated, arginine-starved cancer cells that might have been able to fly under the radar of the immune system might now be waving a tattered red flag at it. This has potential implications for immunotherapy, as starving a cancer cell could promote the gain of new mutations that can then be recognized by the immune system.

The findings of this research have potential implications for cancer treatment, particularly in the context of immunotherapy. By starving cancer cells of arginine, it may be possible to induce the gain of new mutations that can be recognized by the immune system, potentially rendering tumors more vulnerable to the body’s natural immune response.

However, the researchers note that further research is needed to fully understand the mechanisms behind the connection between arginine and cancer, as well as the potential implications for cancer treatment. In the future, this research could inform the development of novel cancer therapies that exploit the vulnerabilities of cancer cells and their reliance on certain nutrients.

Overall, this study sheds light on the complex interplay between cancer cells and their environment, and highlights the potential of nutrient deprivation as a therapeutic strategy for cancer treatment. As our understanding of cancer biology continues to advance, it is hoped that these findings will pave the way for the development of more effective and targeted cancer therapies in the future.

In addition, a ketogenic diet, which is high in fat and low in carbohydrates, may help to create an arginine deficiency and provide a healthier living. This is because the diet restricts the intake of foods that are rich in arginine, such as grains and certain fruits, and instead encourages the consumption of foods that are high in healthy fats, such as avocados and nuts. However, more research is needed to fully understand the impact of a ketogenic diet on arginine levels and cancer treatment.

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