Pancreatic cancer can be reversed with a therapy called “gremlin,” scientists have found in a historical discovery.
Early findings suggest that a gene and protein known as Grem1, or “gremlin,” may be critical to controlling and fighting the disease.
Pancreatic cancer has a notoriously high mortality rate, with only seven percent of patients surviving for five years or more. Every year, more than 10,000 people in the UK are diagnosed with the disease, with around 9,000 dead.
Scientists at the Cancer Research Institute conducted studies in mice and mini pancreas done in a laboratory, where they manipulated the level of gremlin protein in the system.
When the gene, and therefore the protein, was removed, the tumors quickly became a more dangerous and invasive form.
Within days, each tumor cell had become in the most harmless way the most dangerous mesenchymal cancer cells.
The absence of “gremlin” also meant that the cancer was more likely to spread to other organs. In nine out of 10 mice without a gremlin, for example, the cancer spread from the pancreas to the liver.
In contrast, when the gremlin protein functioned normally, the cancer spread to only 15% of laboratory animals.
In addition to reducing Grem1 production, the scientists also increased the protein concentration well beyond the normal level and found that this had a beneficial effect.
Gremlin therapy can “reverse the fate” of dangerous cells
In their study, published in Nature, the scientists said that in high amounts, the gremlin protein “caused an almost complete reversal” of cells that had already been transformed into the most dangerous disguise.
This, they said, indicated that high Grem1 activity was able to “reverse the fate” of dangerous cells.
Subsequent analysis revealed that Grem1 is also controlled by another chemical, called BMP2, and that this molecule regulates the amount of gremlin protein that is made.
The two molecules work together to control how pancreatic cancer develops as part of what researchers call a “self-inhibiting feedback loop.” The mathematical principles underpinning this were first predicted by Alan Turing 70 years ago, a few years after he had broken Enigma and helped defeat the Nazis.
“More studies will be needed to investigate whether the Turing model extends to other types of cancer,” the researchers wrote.
Researchers hope that discovering this link and mechanism, as well as the fact that it can be controlled and reversed, may allow future treatments to be developed to help cure pancreatic cancer.
Although it is still in an early stage and needs a lot of future research and funding, the researchers said it is a crucial first step in fighting what is one of the deadliest forms of cancer.
‘Important and fundamental discovery’
Professor Axel Behrens, leader of the Cancer Stem Cell team at the London Cancer Research Institute, was the lead author of the study and said: “This is an important discovery and fundamental that opens a new avenue to discover treatments for pancreatic cancer.
“We have shown that it is possible to reverse the cellular fate of pancreatic cancer in the laboratory: reverse the clock of aggressive tumors and change them to a state that makes them easier to treat.
“By better understanding what drives the aggressive spread of pancreatic cancer, we now hope to exploit that knowledge and identify ways to make pancreatic cancer less aggressive and more treatable.”
Professor Kristian Helin, executive director of the institute, said: “Pancreatic cancer is one of the most devastating of all cancers: the most common form of the disease is spreading aggressively, making treatment difficult and a diagnosis terrifying for patients and their loved ones.
“This new finding has broadened our understanding of the molecular basis of how pancreatic cancer gains the ability to grow and spread throughout the body.
“While more work is needed, this type of fundamental research is essential to developing concepts for new and more effective treatments for cancer.”
“Improved understanding of the origins of pancreatic cancer”
Dr Chris MacDonald, Head of Research at Pancreatic Cancer UK, told The Telegraph: “While this research is still in its infancy, these exciting new findings represent a large body of work by leading thinkers in this field. which improve our understanding of the origins of pancreatic cancer.
“The ability to spread rapidly throughout the body before it is detected makes it a truly devastating disease. Tragically, 80% of people currently receive a terminal diagnosis.
“We have known for a long time that there are different populations of cells that initiate pancreatic cancer: some that cause very aggressive cancer, and others that produce a more stable form with less chance of spreading.
“This research has shown the potential to actively switch pancreatic cancer cells to the less aggressive form, limiting the disease to the pancreas where it can be more easily addressed with surgery and focused therapies we currently have in our armory.
“This could give many more people the best chances of survival and more precious time with their loved ones.”