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Understanding pancreatic cancer, one gene at a time

UC researcher investigates various mutations in pancreatic cancer to find targeted ways to treat it

Krushna Patra’s life research goal is to cure pancreatic cancer.

“This devastating cancer is difficult to diagnose at early stages of development, and there are limited effective treatment options available,” he says.

To do this, he’s creating models to help study variations of the disease and find the best possible treatment for each mutation involved in its development.

Patra, PhD, an assistant professor in the University of Cincinnati College of Medicine Department of Cancer Biology, was recently awarded a $200,000 Career Development Award from the Pancreatic Cancer Action Network (PanCAN) to fund his projects.

Patra, along with UC colleague Xiaoyang Qi, PhD, who are both members of the UC Cancer Center, was just one of 10 national winners of a 2020 PanCAN research award.

Krushna Patra in his lab holding up a vial

Krushna Patra, PhD, an assistant professor in the University of Cincinnati College of Medicine Department of Cancer Biology, was recently awarded a $200,000 Career Development Award from the Pancreatic Cancer Action Network to fund his research, examining the genetic mutations causing pancreatic cancer. Photo/Colleen Kelley/UC Creative + Brand

“I started my career looking at a cancer-causing gene, called KRAS, KRAS in lung cancer,” says Patra, who came to UC from Harvard last fall. “[The same gene] is actually found in around 93% of pancreatic cancer cases. So, I began to wonder just how many other mutations were occurring within pancreatic cancer and what types of treatments would work best to target these particular variations of the cancer.”

Patra says he is broadly interested in studying genetic mutations in pancreatic cancer, but one of his current “pet projects” is in mutations of a different gene, called GNAS, which is responsible for causing pancreatic cancer that develops from pancreatic cysts.

“These cysts are found in the pancreas and are not cancerous to start, but they are concerning because in some cases they can turn into cancer; many people aged 70 and older have these types of cysts,” Patra continues. “As the malignant nature of these cysts are uncertain, they are either over or undertreated in the clinic.

“We know that when [gene] mutations co-exist, they already show worrisome features, but we don’t know what else is involved in turning them cancerous. If we can discover this, we could determine if a patient should have them removed as a precautionary measure, preventing cancer development altogether.”

Krushna Patra in his lab

“We are interested in uncovering unique pathways established by specific gene mutations in cancer cells. Hopefully, we will eventually be able to come up with more targeted treatments for patients,” says Krushna Patra, PhD. Photo/Colleen Kelley/UC Creative + Brand

Patra realized there was no way available to study this type of pancreatic cancer mutation in the lab, but now, through his innovation, he was one of the first to replicate in animal models the GNAS mutant pancreatic cancer that mimics human disease. His model also shows GNAS is not only required for cystic tumor formation, but also for tumors to survive.

He believes that knowledge of the gene mutations causing pancreatic cancer can be gained if studied in the right model systems. His lab is now trying to create additional models, called organoids, by growing tumors in laboratory cultures and in human samples, enabling him and others to study various types of pancreatic cancer.  

“We are interested in uncovering unique pathways established by specific gene mutations in cancer cells. Hopefully, we will eventually be able to come up with more targeted treatments for patients,” he says. “My lab will also continue looking at the other cells in a tumor’s environment — what’s around them where they ‘live’ — to determine what role it might play on tumor formation and sustainability.”

Several years ago, I was giving a talk to donors about my research. As it ended ... a person approached me and told me that he has premalignant cysts of the pancreas ... And that’s why I do what I do. At that moment, I saw how my work could help people one day. It put a face with the condition.

Krushna Patra, PhD

Patra says the collaborative environment at UC is a wonderful place to do this meaningful work.

“Working with my clinical counterparts, including Dr. Syed Ahmad and other colleagues at the UC Cancer Center, we will continue to try to understand this devastating disease better and find out targets for precision medicine around multiple mutations of pancreatic cancer,” he says.

“Several years ago, while I was still at Massachusetts General Hospital, I was giving a talk to donors about my research, particularly my focus on GNAS mutations in cystic pancreatic cancer,” he adds. “As it ended, the room started to empty, but one person remained — this doesn’t usually happen with a basic science talk. This person approached me and told me that he has premalignant cysts of the pancreas. He asked me what we have learned about this kind of pancreatic cancer and wanted to know more about clinical trials and treatments. And that’s why I do what I do. At that moment, I saw how my work could help people one day. It put a face with the condition.

“It made it all a bit more real.”

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The University of Cincinnati is classified as a Research 1 institution by the Carnegie Commission and is ranked in the National Science Foundation's Top-35 public research universities. UC's graduate students and faculty investigate problems and innovate solutions with real-world impact. Next Lives Here.