Research Grant: How Mutations Help Pancreatic Cancer Grow

Patra has studied a number of genetic abnormalities associated with pancreatic cancer, including a gene
called GNAS.
The daily function of the GNAS gene is to maintain glucose levels in the body and assist in normal development, but when mutated, it becomes overactive and leads to cancer
.

GNAS mutations are present in about 8 to 9 percent of all advanced pancreatic cancers, but if other mutations are present in the lesion, it plays a greater role
in cancers that develop from pancreatic cysts.

Patra, a researcher at the University of Cincinnati Cancer Center, said: "Pancreatic cysts are similar to ovarian cysts in that they have the potential to develop into full-blown cancer, while GNAS mutations are found
in 50 to 60 percent of precancerous growth.
"

Cystic pancreatic tumors are very common in healthy people over the age of 70, Patra said, although not all cysts develop pancreatic cancer
.
But unlike other forms of pancreatic cancer, cystic pancreatic cancer can be detected at a very early stage, providing opportunities
for early intervention and treatment.

"If we understand the effects of this GNAS mutation, we can develop treatments or recommend surgical intervention in certain patients, which could prevent the worst outcomes
," Patra said.

Patra previously developed one of
the first animal models to replicate GNAS-mutated pancreatic cancer.
With this model, his team learned that when GNAS mutations are present in pancreatic cancer, it plays a role
in tumor initiation, progression, and maintenance.
Specifically, GNAS alters the metabolism of cancer cells, and GNAS-mutated pancreatic cancer develops a unique metabolic pathway
compared to other pancreatic cancer subtypes.

"This NCI award will allow us to recruit talented graduate students and postdocs in the lab to study how GNAS alters gene expression and alters mitochondrial structure and function to help tumors grow
," Patra said.