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Scientists from three different American universities simultaneously published three fundamental discoveries regarding pancreatic cancer. Three studies and a better understanding of the disease, which are reviving hope in the fight against this aggressive cancer.
Rare but serious, pancreatic cancer is a so-called silent disease: its progression is quiet, in the absence of symptoms, and very often proves to be very difficult to manage once it is actually detected. This stealthy nature, in fact, attracts scientists who seek to better prevent, detect and treat this disease.
A new starting point for treating pancreatic cancer
It is in this context that scientists from the University of Florida have discovered a way to reverse a key cellular process involved in its progression: they have identified two small molecules that inhibit the progression of precancerous cells. The molecules also reversed a process known as acinar duct metaplasia, or “ADM,” which precedes pancreatic cancer. “To our knowledge, this is the first time that researchers have been able to pharmacologically reverse ADM”, said Tom Schmittgen, lead author of the study and chair of the UF Department of Pharmacy. The finding was published in the journal Cell Death Discovery, last September.
As the study explains, ADM often occurs when inflammation is present. It is a defense mechanism to prevent the pancreas from producing too many digestive enzymes and destroying itself. During ADM, stable, enzyme-producing acinar cells transform into protective duct cells that line the pancreatic duct. However, if certain genes mutate during the transition, the cells can become precancerous and eventually develop into cancer.
To study ADM, the scientists therefore built a laboratory model using animal cells with pancreatic cancer and tissue from a healthy human being. They introduced the cells into two compounds. The ductal cells responded positively by becoming acinar cells again.
“With these compounds, we could potentially treat a patient with pancreatic cancer at an early stage of the disease and hopefully improve the treatment options available.” predict the researchers. “This research could lead to the development of treatments for patients at high risk of developing pancreatic cancer.”.
An updated bacterium in the functioning of this cancer
Evidence of active research in the field of pancreatic cancer, another study, this time from the Department of Biomedical Engineering at Virginia Tech and published on October 18 in the journal Science Signaling can better target how bacteria make pancreatic cancer cells grow and move. These researchers discovered a characteristic of a common oral bacterium that travels to cancerous tumors in the pancreas, called Fusobacterium nucleatum, which could play a key role in how aggressively the cancer grows and travels throughout the body.
Because this microbe is a common oral bacterium, it has often been studied in relation to diseases of the mouth such as periodontitis and gingivitis. But little was known about how the microbe moves and adapts to life in tumor microenvironments. Using in vitro tumor-on-a-chip models, the team observed and confirmed that this microbe can also bind and invade pancreatic cancer cells, which then secrete molecules that stimulate the accelerated growth of cancer cells to produce a number much higher than expected.
Any cell infected with the microbe could then potentially be more susceptible to cancerous growth at a later time, or even more prone to metastasis, the researchers suggest. If this study does not promise today to put an end to this cancer, the discovery is important: by understanding how the bacteria present in tumors affect the growth and the spread of cancer, scientists could design treatments of chemotherapy or more effective immunotherapy.
“The next steps will be to set up studies that can tell us if this knowledge is interesting leads for developing more effective therapies, adapted to the components of a patient’s microbiome.” conclude the researchers.
Radioactive tumor implant dissolves tumors in mice
Finally, the latest study on the subject conducted by Duke University in North Carolina is just as striking: the scientific team would have simply developed a new treatment which would have completely eliminated tumors in 80 % of mice included in their preliminary study, on several types of models, including those considered the most difficult to treat.
Their approach, which combines traditional chemotherapy drugs with a new method of irradiating the tumor, relies on the introduction of radioactive iodine-131 directly into the tumor in a gel-like depot (a substance made up of elastin type PEL) which protects healthy tissue and is absorbed by the body after the radiation has disappeared.
The researchers tested their approach on mice with cancers just under the skin, created by several different mutations known to occur in pancreatic cancer. They also tested it on mice that had tumors in the pancreas.
Overall, the tests recorded a 100% response rate across all models, with tumors completely cleared in three-quarters of the models about 80% of the time. The tests also revealed no immediately obvious side effects beyond what is caused by the chemotherapy alone. “This makes us think that this approach might actually work better than external beam therapy for many other cancers as well.” reacted Jeff Schaal, the lead author of the study.
The approach, however, is still in its early preclinical stages and must already go through larger animal testing before considering human testing. However, it leaves the door open to new possibilities.
As a reminder in France, pancreatic cancer affects approximately 14,000 people per year, according to the latest figures, with a largely unfavorable vital prognosis (only 11% at 5 years).