Recent research carried out by investigators at the Salk Institute (CA, USA) and published in Cell has demonstrated that a synthetic derivative of vitamin D has the potential to increase the susceptibility of pancreatic cancer to chemotherapy and other cancer treatments.
The research demonstrated that the derivative has the ability to destroy the barrier of cells surrounding pancreatic tumors. Following destruction of the barrier of cells, the researchers found that the pancreatic tumors were more susceptible to therapeutic drugs. The findings have led to human clinical trials of the compound in the treatment of pancreatic cancer.. The team hope that the findings could also translate to other cancers such as; lung, liver and kidney.
“While the success of this drug in humans with pancreatic cancer is still unclear, the findings in animal studies were strong, raising hope that ongoing clinical trials will give people with this terrible disease hope for a truly new type of therapy,” explained Ronald Evans (Salk Institute).
“For pancreatic cancer, the 5-year survival rate is the lowest of all cancers,” continued Evans. “Part of the problem is that the science of pancreatic cancer and its renowned resistance to therapy has not been understood and that’s why the work that we’re doing is so important.”
The researchers demonstrated that disruption of the tumor microenvironment with their vitamin D-like compound allowed tumors, which are usually protected by this barrier of cells, to be destroyed with chemotherapeutic drugs or immune cells. The compound is known to affect the stellate cells near the tumor, which are in a state of chronic activation in pancreatic cancer. Activated pancreatic stellate cells near a tumor were discovered to have elevated vitamin D receptors levels. Addition of the modified compound to the activated stellate cells prompted the cells to revert back to their inactivated state.
“This was a big surprise because vitamin D has been tried multiple times as a therapy for pancreatic cancer and never worked,” reported Evans.
“There was evidence that the activation of the microenvironment was theoretically reversible, but nobody knew exactly what was responsible for the activation, making it hard to turn off,” explained Mara Sherman (Salk Institute).
The researchers then investigated the ability of the compound to prevent the growth of a tumor. Utilizing mice models, the researchers demonstrated that combining the synthetic derivative with existing chemotherapeutics gave a 50% increase in lifespan compared with chemotherapy alone.
“It’s really remarkable considering that vitamin D itself is not attacking the cancer cells,” commented Michael Downes (Salk institute) “It’s changing the environment to a more favorable setting needed for the chemotherapy drugs to work.”
“Recently, other research groups have explored the idea of destroying the microenvironment altogether to weaken a tumor,” continued Downes. “Our approach is very different. Instead of destroying, we simply want to reprogram the tumor microenvironment to a healthy state. This has the dual effects of delivering more drugs to the tumor as well as replenishing the tissue with normal stellate cells.”
The researchers are now collaborating with clinicians at the University of Pennsylvania (PA, USA) to investigate the effectiveness of the synthetic derivative of vitamin D in cancer patients prior to pancreatic surgery. “Previous trials with vitamin D failed because they didn’t understand the need for a special form of vitamin D and that for pancreatic cancer it must be used in combination with chemotoxic drugs,” Evans explained. “So, by rethinking the problem, have been able to open up a new route to the treatment of pancreatic cancer and, looking forward, hopefully other diseases as well”.