Pancreatic cancer is one of the most difficult cancers to treat, in part because it’s often asymptomatic in its earliest stages, when treatment can do the most good. But that’s not the only thing that makes pancreatic cancer treatment tricky. The pancreas has evolved a unique way to protect itself from injury and infection — but one that, conversely, allows cancerous tumors to grow unchecked by either the immune response or chemotherapy drugs. Researchers at the Salk Institute think they’ve found a way to get around this obstacle, using a derivative of vitamin D.
Why Chemotherapy Can’t Touch Pancreatic Cancer
Under normal conditions, when a cancerous cell appears in the body, the immune system kills it right away. That’s a key part of its function. But when cancer cells appear in the pancreas, the immune system can’t get to them, thanks to the action of pancreatic stellate cells (PSCs).
When the pancreas sustains an injury or infection, PSCs surround it and “start excreting a lot of extracellular matrix that acts like cement,” according to Salk Institute researcher Michael Downes, PhD. This tough extracellular barrier keeps the infection or damage from spreading. In the case of a non-cancerous injury or infection in the pancreas, this is a good thing. It protects the rest of the pancreas from damage and promotes faster healing.
But when the “injury” is not, in fact, an injury but a cancerous tumor, the extracellular barrier becomes more trouble than it’s worth. Instead of protecting the rest of the pancreas from spreading cancer, the barrier instead manufactures the exact conditions pancreatic cancer needs to flourish. It blocks immune cells from destroying pancreatic cancer in its earliest stages. Later on, it stops chemotherapy drugs from getting to the cancer cells, making the cancer harder to treat. That’s why SBRT, which delivers a focused beam of potent radiation directly to the tumor itself, remains one of the most effective ways to treat pancreatic cancer.
Breaking Down the Extracellular Barrier
For some time now, scientists have suspected that vitamin D may be capable of breaking down the extracellular matrix PSCs erect around pancreatic tumors, allowing chemotherapy drugs to attack the cancer cells more effectively. But even when it’s riddled with cancer, the pancreas breaks down natural vitamin D so quickly that it can’t do much good against the extracellular matrix.
Now, however, researchers at the Salk Institute think they’ve found a vitamin D derivative that the pancreas can’t break down as quickly. The researchers administered this modified version of vitamin D, called Calcipotriol, along with chemotherapy to mice with pancreatic cancer. Compared with a control group of mice who received just chemotherapy, the mice who received Calcipotriol lived 57 percent longer. Three in 10 of the mice who received Calcipotriol plus chemotherapy with a drug called gemcitabine were considered “long-term” survivors. Those three mice lived an average of three to four times longer than the mice who just received gemcitabine.
The results are so promising that the FDA has already approved human trials to determine how safe Calcipotriol is for use in humans with pancreatic cancer and what dosages to administer for this purpose. Researchers at the Translational Genomics Research Institute in Phoenix and the University of Pennsylvania are already conducting early human trials, funded by the group “Stand Up to Cancer.”
Calcipotriol has already been approved by the FDA for the treatment of psoriasis. Researchers first got an inkling that it might be useful for de-activating PSCs when they realized that it could be used to de-activate the stellate cells responsible for creating liver fibroids in chronic liver disease. When the researchers began studying the mechanisms responsible for activating PSCs, they realized that PSCs have a lot of vitamin D receptors, and theorized that vitamin D might play a role in activating or de-activating PSCs. Further research showed that a synthetic form of vitamin D might be capable of reversing the effects of PSC activation in pancreatic cancer.
Pancreatic cancer researchers have known for some time that vitamin D might have a role to play in treating pancreatic cancer, but they needed to come up with a synthetic type of vitamin D that wouldn’t be immediately metabolized by the pancreas. They ultimately settled on Calcipotriol, a drug used to treat psoriasis. Soon, a combination of Calcipotriol and chemotherapy could be a powerful weapon in the arsenal against pancreatic cancer.