Researchers from UC Davis Cancer Centre have identified a metabolic deficiency in pancreatic cancer cells that can be used to slow the progression of one of the most fatal cancers.
They have found that pancreatic cancer cells cannot produce the amino acid arginine, which plays an essential role in cell division, wound healing, immune function and hormone regulation.
AdvertisementBy depleting arginine levels in cell cultures and animal models, the team was able to significantly reduce pancreatic cancer-cell proliferation.
"There have been few significant advances in 15 years of testing available chemotherapy to treat pancreatic cancer," said Richard Bold, chief of surgical oncology at UC Davis and senior author of the study.
"The lack of progress is particularly frustrating because most patients are diagnosed after the disease has spread to other organs, eliminating surgery as an option. We have to turn back to basic science to come up with new treatments," he added.
The research team led by Bold hypothesized that pancreatic cancer cells lack the ability to produce arginine.
In human pancreatic tumours, they measured levels of an enzyme, argininosuccinate synthetase, required to synthesize arginine.
The enzyme was not detected in 87 percent of the 47 tumour specimens examined, suggesting that the majority of pancreatic cancers require arginine for cell growth because of an inability to synthesize the amino acid.
The researchers then conducted further tests using pancreatic cell lines that represent the varying levels of argininosuccinate synthetase observed in human tumor specimens.
The researchers depleted arginine levels in cultures of pancreatic cell lines using arginine deiminase, an enzyme isolated from Mycoplasma bacteria.
The researchers found that exposing the pancreatic cancer cell lines to the modified arginine deiminase enzyme inhibited cancer-cell proliferation by 50 percent.
They then treated mice bearing pancreatic tumors with the same compound and found an identical outcome a 50 percent reduction in tumor growth.
According to Bold, the current study represents a unique approach to cancer treatment in that it is one of the first to identify a metabolic pathway that can be leveraged to interrupt cancer growth.
The research is published in International Journal of Cancer.