Pancreatic Cancer Awareness Month: New Drugs, New Approaches, New Science Underpins Approach
The pancreas is approximately the size of a hand and lies across the upper abdomen, actually behind the lower part of the stomach. Its job in the body is to manufacture insulin and enzymes for digestion.
Pancreatic cancer is currently rated as the third-leading cause of cancer-related deaths in the U.S., and is projected to be the second by 2020.
It’s a notoriously difficult cancer to treat and is typically diagnosed so late in the game that it has metastasized throughout the body. The statistics aren’t good. Approximately 55,440 individuals are expected to be diagnosed in the U.S. this year and 44,330 will die from it. Only about 8.5 percent of people diagnosed with pancreatic cancer survive for five years.
Yet, for all the bleakness, many researchers think they are on the cusp of significant breakthroughs for both diagnosis and treatment of pancreatic cancers.
Pancreatic cancer, like almost all cancers, is not a single disease. For example, neuroendocrine tumors, which are the type that both Aretha Franklin and Apple founder Steve Jobs died from, are rare types of pancreatic cancer.
A drug marketed by Novartis, Afinitor, has some positive effect on neuroendocrine tumors that have spread outside the pancreas, slowing the initiation of tumor growth from about six months to 11.6 months.
The more common form of pancreatic cancer, adenocarcinoma, has an even worse prognosis. It is the type of cancer that took the lives of Dirty Dancing actor Patrick Swayze and opera singer Luciano Pavarotti.
For adenocarcinomas, there are generally two chemotherapy regimens. One is a combination of Gemzar and Abraxane, and the other is a cocktail of drugs called FOLFIRINOX. They extend survival from about four months to nine months in the average patient.
Surgical removal of the tumor when it’s small gives the best odds of survival. But that’s not often possible. Nicole Fawcett, writing for the University of Michigan Health Lab Blog, says, “It grows in an unusual pattern in which tentacles extend into the nerves and blood vessels. This creates challenges for surgeons and radiation oncologists who must work around these critical structures. It’s one reason only 20 percent of patients can have surgery.”
It also metastasizes quickly. And because symptoms are often generic—back pain, unexplained weight loss, jaundice—the cancer is typically detected late. There are no particular early-screening tests, although researchers at the University of Michigan’s Rogel Cancer Center are working on detecting circulating tumor cells or RNA markers of the cancer in the blood. Other techniques being investigated include creating a “scaffold device” inserted into the body that could set off an early warning of a developing pancreatic tumor.
Once biotech startup, Nivien Therapeutics, which spun out of Harvard University research, is working on an approach to treating the disease based on a biochemical system called Hippo. Hippo controls a group of proteins, including CDA and ABCG2, that are involved in cancer metabolism and removal of chemotherapy agents inside the cell.
Another biotech company, which came out of stealth mode in June 2017, is Vivace Therapeutics, which is also working on the Hippo-YAP signaling pathways. It is working on novel therapeutic antibodies called BINSpecific antibodies, that bind in an almost irreversible and cell-type specific manner to target cells.
And Halozyme Therapeutics is working on developing PEGPH20, which breaks through the stroma to allow chemotherapy into the tumor. The technology the company uses is ENHANZE drug-delivery, based on a patented recombinant human hyaluronidase enzyme (rHuPH20). The gist of the technology is that it allows cancer drugs better access to cancers that tend to have structures that prevent chemical access.
Pancreatic cancer is a tough nut to crack, and researchers are taking many different approaches to find treatments. One approach is what researchers have dubbed “phase minus-1.” That refers to preclinical research, but the “minus 1” part refers to not just animal models, but “human three-dimensional organoid models” running concurrently.
There is quite a bit of work going on, some of it related to 3D bioprinting, to develop 3D living tissues and organs that can be used in research and clinical trials. One is InVivo, which developed micro-engineered heart tissues, now called NuHeart.
Howard Crawford, director of the Pancreas Disease Initiative and professor of molecular and integrative physiology and internal medicine at U of M, told Fawcett, “The pancreatic cancer field in general is a very collaborative group. This is such a bad disease. It doesn’t matter who makes progress. Research funding for pancreatic cancer is very low, but beyond just money we need a smart approach to understanding this disease.”