Big Ideas

Costas Lyssiotis, Ph.D.

As new cancer treatments emerge and survival rates continue to rise, pancreatic cancer has stubbornly refused to adhere to these positive trends. The five-year survival rate is a meager 10%, a statistic that has barely budged in the past 30 years. Why has there been so little progress in the fight against pancreatic cancer? Costas Lyssiotis, Ph.D., and the team of pancreatic cancer scientists and clinicians in the Pancreatic Disease Initiative at the University of Michigan Rogel Cancer Center are finding some answers.

Pancreatic cancer has remained an enigma to researchers for several reasons. The most obvious is that since pancreatic tumors grow in the middle of your body, they can remain asymptomatic for longer than many others, so cancer is often much farther advanced when it is discovered. However, that isn’t the sole reason for the distressing data.

Pancreatic tumors are made up of primarily non-cancer support cells, and these cells foster a scarring reaction that forms a fortress of sorts around the tumor. This scarring, technically known as the fibroinflammatory response, limits the ability for drugs to penetrate the tumor and is thought to be the reason why new immunotherapies don’t work for pancreatic cancer.

Lyssiotis and his team are focused on deciphering how the microenvironment of these tumors helps them resist treatments. Their research has revealed that, in addition to making it physically harder for drugs to reach the tumor, the non-cancer support cells provide cancer cells with nutrients. Lyssiotis’ hope is that by studying this process, the team can find a way to block the flow of nutrients and starve the cancer cells.

“A solid tumor mass isn’t just a bunch of cancer cells,” said Lyssiotis, a 2016 V Scholar recipient. “You have all these other cell types working together with the malignant cells to instruct it on how to survive, grow and resist therapy. So we are investigating the mechanisms by which metabolism, the access to and utilization of nutrients, supports the growth and therapeutic resistance of this mass.”

As part of their quest to interrupt this feeding process, the team is also looking at the relationship between the cancer cells and the immune system. Immune cells require nutrients to gain the energy needed to kill cancer cells, but they are often being out-competed by nutrient-hungry cancer cells. Lyssiotis’ team is searching for ways to shift the flow of nutrients away from cancer cells and toward immune cells. In addition to boosting the body’s natural cancer defenses, this could also pave the way for immunotherapies that actually work against pancreatic cancer.

“If you block the ability of the cancer cells to appropriate these fuels, the anti-tumor immune cells are much better at killing the tumor,” said Lyssiotis. “By facilitating access to nutrients, we anticipate that the anti-tumor immune system will be primed to respond to other immune-based therapies, and together these will potently recognize and kill cancer cells.”

These discoveries are welcome news, given the dire nature of most pancreatic cancer diagnoses. People fully invested in this field, like Lyssiotis, know their work could be key to improving some of the grimmest statistics of any cancer type.

“If you have a late stage diagnosis, the odds that you’re going to live out half a year are only around 20%, which is a brutal statistic,” said Lyssiotis. “It’s one that keeps me up at night.”

Lyssiotis said he hopes his research and that of others in the field will get these statistics moving in the right direction. And he is optimistic that down the road, a pancreatic cancer diagnosis will be a challenge but not a death sentence.