New Review in CMJ Highlights Role of Arginine Metabolism in Pancreatic Cancer and its Treatment

SHANGHAI, Sept. 15, 2021 /PRNewswire/ -- Although the battle against cancer has been fought by the medical and scientific community with much vigor, almost every day it brings about a new conundrum. Recent studies have implicated that arginine, a "conditionally essential" amino acid that the body requires to make important proteins, plays an important role in the life cycle of cancer cells. This is good news when it comes to its potential therapeutic applications—as detailed in a recent review article, by a team of scientists from China, published in Chinese Medical Journal.

The research group has collated studies on the role of arginine metabolism in pancreatic cancer and potential therapeutic approaches in a comprehensive review. Dr. Lei You, the corresponding author of the article, says, "In this review, we introduce arginine metabolism and its impacts on pancreatic ductal adenocarcinoma cells. Also, we discuss the role of arginine metabolism in arginine deprivation therapy and immunotherapy for cancer."

The review focusses on pancreatic ductal adenocarcinoma (PDAC), an extremely malignant form of pancreatic cancer with a low survival rate. The PDAC cells use a notable strategy called "metabolic reprogramming," which enables the cancer to progress without control. The team has narrowed down a key contributor in this strategy – arginine.

PDAC cells exhibit altered arginine metabolism, which in turn affects several important signaling pathways. Moreover, arginine gets biochemically converted into various metabolites which aid the multiplication, growth, "self-eating" or autophagy, cell death, and metastasis (spread to other organs) of PDAC cells.

However, PDAC cells lose the ability to synthesise arginine on their own due to loss of the enzyme "argininosuccinate synthetase 1." This scenario can be exploited as a therapeutic opportunity – "starving" PDAC cells of arginine can curb the unchecked cancer. In fact, studies have successfully employed this therapeutic strategy. Alternatively, targeting arginase 1, the enzyme which converts arginine to ornithine, thereby reducing arginine levels, has been shown to suppress cancer growth. Given its role in immune responses, this strategy can also be applied in immunotherapy.

Drug resistance, re-expression of argininosuccinate synthetase 1 enzyme and expression of "anti-drug" antibodies can however, act as speed bumps in the aforementioned therapies. To overcome this hurdle, the researchers propose arginine-deprivation drugs in combination with other drugs. Dr. You concludes by saying, "We believe that arginine deprivation combined with other reagents therapy such as gemcitabine or immunotherapy is still a potential method to overcome cancer, but this emergently needs more basic and clinic studies."

The review indeed serves as a useful roadmap for future advancements in the treatment of pancreatic cancer.

Reference

Titles of original papers: Arginine metabolism: a potential target in pancreatic cancer therapy

Journal: Chinese Medical Journal

DOI: https://doi.org/10.1097/CM9.0000000000001216

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SOURCE Chinese Medical Journal