Although progress has been made in treating the disease, it’s still often fatal, and is made up of multiple diseases.
The recent news that “Jeopardy” game show host Alex Trebek was diagnosed with stage 4 pancreatic cancer has again focused the public’s attention on this difficult-to-treat disease. And it was less than a year ago when famed singer Aretha Franklin died from a neuroendocrine tumor of the pancreas.
Although progress has been made in treating the disease, it’s still often fatal, and like cancer in general, is not a single disease.
But researchers at Cold Spring Harbor Laboratory in New York may have found an important piece to the puzzle. David Tuveson and Danielle Engle were working on a possible biomarker test for pancreatic cancer when they found that a sugar molecule called CA19-9, which was associated with pancreatic cancer but was thought to be harmless actually plays a significant role in causing it. Their findings were published in the journal Science.
“We studied CA19-9 because we were trying to make it a better biomarker for early detection of pancreatic cancer,” Tuveson told Discover Magazine.
Patients with pancreatic cancer overproduce CA19-9. As it accumulates, it appears to attach to other molecules, changing the structure and function of those proteins.
However, pancreatic cancer cells aren’t the only cells in the human body to produce CA19-9. Tuveson and his research team theorized that by identifying the specific proteins CA19-9 typically attached to, they would be able to find useful biomarkers.
From a laboratory perspective, they had a problem. Mice don’t produce CA19-9, and they needed an animal model to work with. So they genetically engineered laboratory mice that could produce CA19-9.
What they found was that the mice developed inflammation of the pancreas, or pancreatitis. Also, this inflammation sped up pancreatic tumor development. In the mice, CA19-9 appeared to recruit the immune system to repair damage from pancreatitis. It also stimulated a cascade of biochemical reactions that were caused by the release of toxic digestive enzymes from the pancreas. That cascade opened a gateway for cancer to develop. The researchers also found that CA19-9 can significantly accelerate pancreatic tumor growth.
Danielle Engle, lead author of the study and a former postdoctoral fellow at Cold Spring Harbor Laboratory, who is now an assistant professor at the Salk Institute, stated, “This is one of those unique opportunities where prophylactic intervention of pancreatitis may lead to prevention of pancreatic cancer in at-risk patients. Pancreatitis is required for developing pancreatic cancer, and we might be able to prevent that transition in patients with pancreatitis by targeting CA19-9.”
The clinical potential is great. If Tuveson, Engle or anyone else can develop an antibody against CA19-9 that blocks pancreatic inflammation, it might help patients with chronic pancreatitis, and would potentially have benefits in decreasing the risk of pancreatic cancer.
And conveniently, there are already human antibodies to CA19-9. Germany’s BioNTech has exclusive rights to them for the treatment and prevention of pancreatitis, and Tuveson is hopefully they will begin clinical trials. “This paper actually provides the preclinical rationale for conducting such a study,” he told Discover Magazine.
BioNTech acquired MabVax Therapeutics’ Phase I candidate, MVT-5873, an antibody to CA19-9 in May. Positive interim data in 35 patients was announced in February 2018. MabVax is reportedly also developing a CAR-T immuno-oncology therapy that targets CA19.9.
