Yale researchers have found that the overexpression of a protein called renalase in pancreatic cancer plays a critical role in spurring the cancer’s growth while also providing a possible new target for attacking the tumors it helps develop. The findings were described in the March 14th online issue of Scientific Reports.
Pancreatic cancer is one of the deadliest cancers, causing about 40,000 deaths annually in the U.S. It is difficult to detect, and most cases are diagnosed at later stages. While there has been some progress in using chemotherapy against the disease, it remains largely resistant to known therapies. The overall five-year survival rate for patients is less than 5%.
This is why the study’s lead author, Gary Desir, M.D., professor of Medicine, is so encouraged by the findings. Desir is no stranger to renalase, having discovered and named it in 2005 in his Yale lab.
“We discovered renalase while searching for a mechanism that could explain the very high incidence of heart disease in patients with failure,” Desir said. “We named this previously unknown protein that circulated in plasma at very high levels renalase. We chose that name because the kidney (renal) makes a lot of it, and it functions as an enzyme (ase) to metabolize adrenaline.”
From the beginning, Desir and his team were interested in exploring whether renalase in the circulating in the blood could serve as a biomarker for cancer after noting many cancer cells synthesized and secreted it. As they developed methods to synthesize renalase by making antibodies to measure its expression, they determined that it functions as a growth factor with a critical role in pancreatic cancer.
This led to the discovery that renalase’s behavior held clues to its vulnerability as a target for new drugs.
“We have discovered that pancreatic cancer cells misuse the renalase pathway to help them proliferate, and we have developed monoclonal antibodies of renalase that can kill pancreatic cancer cells and treat tumors in mice,” Desir said. “Patient outcomes for pancreatic cancer are dismal, and we’re encouraged by these findings.”
Other study authors were: Xiaojia Guo, Lindsay Hollander, Douglas MacPherson, Ling Wang, Heino Velazquez, John Chang, Robert Safirstein, Charles Cha, and Fred Gorelick