Pancreatic cancer is one of the neoplasms with the worst prognosis because it is generally detected when it is in advanced stages and, furthermore, it is difficult to treat because it has a tendency to develop genetic mutations that make it resistant to available treatments. In fact, although it only represents 3.2% of cancer cases, it is the third leading cause of death from this disease.
Therefore, the results of a new study may represent an important advance in the treatment of pancreatic cancer, since a novel therapeutic option that combines chemotherapy with a radioactive tumor implant has managed to completely eliminate tumors in 80% of mice in different types of pancreatic cancer models, including those that are considered the most difficult to treat.
The research has been carried out by biomedical engineers from Duke University, who have combined traditional chemotherapy drugs with a new technique to irradiate the tumor from within; that is, instead of delivering radiation from an external beam that travels through healthy tissue, they have implanted radioactive iodine-131 directly into the tumor within a gel-like reservoir that protects healthy tissue and is absorbed by the tumor. body after the radiation fades.
“We did a deep dive through more than 1,100 treatments in preclinical models and never found results where tumors shrank and disappeared like ours did,” said Jeff Schaal, who has been involved in the research during his Ph.D. lab of Ashutosh Chilkoti, Alan L. Kaganov Distinguished Professor of Biomedical Engineering at Duke. “When the rest of the literature says that what we’re seeing isn’t happening, that’s when we knew we had something extremely interesting.” The work has been published in Nature Biomedical Engineering.
Constant radiation to the tumor improves the effectiveness of chemotherapy
To get a radiation dose to the tumor high enough to be effective while avoiding serious side effects, Schaal decided to use a substance made from elastin-like polypeptides (ELPs), which are synthetic chains of amino acids that exist in the liquid at room temperature, but form a stable gel-like substance inside the human body that is warmer. When injected into a tumor along with a radioactive element, ELPs form a small reservoir that encloses radioactive atoms. The researchers used iodine-131, a radioactive isotope of iodine, in this case because doctors have been using it in medical treatments for decades and its biological effects are known.
Tumors completely disappeared in three-quarters of animal models of pancreatic cancer about 80% of the time
The ELP depot contains iodine-131 and prevents it from leaking into the body. Iodine-131 emits beta radiation, which penetrates the biogel and deposits almost all of its energy in the tumor without affecting the surrounding tissue. The ELP depot breaks down into its constituent amino acids and is absorbed by the body over time, but not before the iodine-131 has broken down to a harmless xenon form. “Beta radiation also improves the stability of the ELP biogel,” explained Schaal, “that helps the deposit last longer and only breaks down after the radiation runs out.”
Schaal and his collaborators in the Chilkoti lab tested this new therapy along with paclitaxel, a chemotherapy drug, to treat various mouse models of pancreatic cancer to see if their radioactive tumor implant creates synergistic effects with chemotherapy than the chemotherapy drug. radiation beam of relatively short duration does not produce.
The technique was tested on mice with cancers just under the skin created by several different mutations known to occur in pancreatic cancer, and also on mice that had much more difficult-to-treat tumors in the pancreas. Overall, the tests showed a 100% response rate in all models, with tumors completely disappearing in three-quarters of the models approximately 80% of the time. Also, no side effects were seen right away, except for those associated with chemotherapy alone.
“We believe that constant radiation allows drugs to interact with their effects more strongly than external beam therapy does,” Schaal said. “That makes us think that this approach might also work better than external beam therapy for many other types of cancer.”
This new therapeutic alternative is still in its early preclinical stages, so it will not be available for human use in the short term. The study authors have said that they will next need to conduct large-animal trials, which will need to show that the technique can be performed accurately with existing clinical tools and endoscopy techniques already used by clinicians. If this research is successful, its next goal would be a Phase 1 clinical trial in humans.
“My lab has been working on developing new cancer treatments for almost 20 years, and this work is perhaps the most exciting we have done in terms of its potential impact, as late-stage pancreatic cancer is impossible to treat. try and it is invariably fatal,” Chilkot has said. “Pancreatic cancer patients deserve better treatment options than are currently available, and I am deeply committed to bringing this to the clinic.”
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