Engineers at Duke University have developed a novel delivery system for cancer treatment and demonstrated its potential against one of the disease’s most troublesome forms. In newly published research in mice with pancreatic cancer, the scientists showed how a radioactive implant could completely eliminate tumors in the majority of the rodents, demonstrating what they say is the most effective treatment ever studied in these pre-clinical models.
Pancreatic cancer is notoriously difficult to diagnose and treat, with tumor cells of this type highly evasive and loaded with mutations that make them resistant to many drugs. It accounts for just 3.2 percent of all cancers, yet is the third leading cause of cancer-related death. One way of tackling it is by deploying chemotherapy to hold the tumor cells in a state that makes them vulnerable to radiation, and then hitting the tumor with a targeted radiation beam.
But doing so in a way that attacks the tumor but doesn’t expose the patient to heavy doses of radiation is a fine line to tread, and raises the risk of severe side effects. Another method scientists are exploring is the use of implants that can be placed directly inside the tumor to attack it with radioactive materials from within. They have made some inroads using titanium shells to encase the radioactive samples, but these can cause damage to the surrounding tissue.
"There's just no good way to treat pancreatic cancer right now," said study author Jeff Schaal.
Schaal and his team explored an alternative type of implant, one made from more biocompatible materials that wouldn’t post the same risks to the human body. The scientists used synthetic chains of amino acids known as elastin-like polypeptides (ELPs), which remain in a liquid state at room temperature but form a stable gel-like material in the warmer environment of the body.
This substance was injected into tumors in various mouse models of pancreatic cancer along with a radioactive element called iodine-131, an isotope that is well-studied and widely used in medical treatment. In this environment, the ELP entombs the iodine-131 and prevents it leaking into the body, but allows it to emit beta radiation that penetrates into the surrounding tumor. Once the radiation is spent, the ELP biogel safely degrades into harmless amino acids.
The treatment was tested in combination with a common chemotherapy drug called paclitaxel. The radioactive implants were injected into cancer tumors just beneath the skin, but with mutations known to occur in pancreatic cancer, and into tumors within the pancreas itself that are historically more difficult to treat.
Across all the models tested, the scientists report a 100% response rate to the treatment. In three quarters of the models, the dual treatment completely eliminated the tumors 80% of the time. The scientists deployed the novel treatment against pancreatic cancer because they wanted to explore its potential against one of the trickiest forms of the disease, but believe these results bode well for its wider application.
"We think the constant radiation allows the drugs to interact with its effects more strongly than external beam therapy allows," Schaal said. "That makes us think that this approach might actually work better than external beam therapy for many other cancers, too."
There is lots to play out before that happens, with trials on larger animals the immediate next step for the researchers. They do say these findings are unparalleled in terms of how effectively the treatment was able to disintegrate the tumors, with team member Ashutosh Chilkoti describing them as “perhaps the most exciting” results against late-stage pancreatic cancer his lab has produced in almost 20 years.
"We did a deep dive through over 1,100 treatments across preclinical models and never found results where the tumors shrank away and disappeared like ours did," said Schaal. “When the rest of the literature is saying that what we're seeing doesn't happen, that's when we knew we had something extremely interesting."
The research was published in the journal Nature Biomedical Engineering.
Source: Duke University via MedicalXpress
