UC Davis Cancer Center researchers have discovered a metabolic deficiency in pancreatic cancer cells that can be used to slow the progress of the deadliest of all cancers.
Published in the October issue of the International Journal of Cancer , study results indicate that pancreatic cancer cells cannot produce the amino acid arginine, which plays an essential role in cell division, immune function and hormone regulation. By 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."
Bold explained that average survival time for those diagnosed with pancreatic cancer is just four-and-a-half months, although chemotherapy can extend that prognosis up to six months.
"There is a dire need to find new options for these patients. While our findings do not suggest a cure for pancreatic cancer, they do promise a possible way to extend the life expectancies of those diagnosed with it," Bold said.
Bold and his colleagues hypothesized that pancreatic cancer cells lack the ability to produce arginine. In human pancreatic tumors, they measured levels of an enzyme - argininosuccinate synthetase - required to synthesize arginine.
The enzyme was not detected in 87 percent of the 47 tumor 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. Focusing on the lines with lowest levels, the researchers depleted arginine levels in cultures of pancreatic cell lines using arginine deiminase, an enzyme isolated from a Mycoplasma bacteria.
The enzyme was modified by adding polyethylene glycol chains to increase size and circulatory time.