Nature: Easily remove gels from mouse pancreatic cancer

Advanced pancreatic cancer is impossible to treat and is always fatal
.

Biomedical engineers at Duke University have demonstrated the most effective treatment
for pancreatic cancer to date in mouse models.
While most mouse trials suggest that simply stopping growth can be successful, the new treatment completely eliminated 80 percent of the tumors in several model types of mice, including those considered the most difficult to treat
.

The method combines
traditional chemotherapy drugs with a new method of tumor irradiation.
Instead of delivering radiation to healthy tissue through an external beam, the treatment implants radioactive iodine-131 directly into a tumor gel-like reservoir that protects healthy tissue and is absorbed
by the body after the radiation wears off.

The findings were published Oct.
19 in
the journal Nature Biomedical Engineering.

Jeff Schaal, who conducted the study during his PhD in the lab of Ashutosh Chilkoti, the Alan L.
Kaganov Principal Professor of Biomedical Engineering at Duke University, said, "We have conducted in-depth research on treatments in more than 1100 preclinical models and have never found tumors shrinking and disappearing
as much as ours.
When other literature says that what we saw didn't happen, we know we found something very interesting
.
”

Despite accounting for only 3.
2% of all cancer cases, pancreatic cancer is the third leading cause
of cancer-related death.
It is very difficult to treat because its tumors tend to develop aggressive genetic mutations that make them resistant to many drugs, and are often diagnosed late, by which time it has spread to other parts of
the body.

Current leading treatments incorporate chemotherapy, which keeps cells in a reproductive phase susceptible to radiation for a longer period of time, while emitting a beam of radiation
against the tumor.
However, this approach is ineffective unless a certain radiation threshold reaches the tumor
.
Despite recent advances in the shaping and aiming of radiation beams, it is difficult to reach this threshold
without risking serious side effects.

Another method the researchers tried was to implant a radioactive sample wrapped in titanium directly into the
tumor.
But because titanium blocks all radiation except gamma rays, which travel far beyond the tumor, it can only stay in the body for a short period of time
before the surrounding tissues are damaged.

Schaal is now the head of research at Cereius, a biotech startup in Durham, North Carolina, focused on commercializing
targeted radionuclide therapies through different technology solutions.

To sidestep these problems, Schaal decided to try a similar implant method, using a substance made from elastinoid peptides (ELPs) that are held together by synthetic chains of amino acids to form a gel-like substance
with customized properties.
Since ELPs are a focus of Chilkoti's lab, he was able to work with his colleagues to design a transmission system
that was ideally suited for the task.

ELPs exist in a liquid state at room temperature, but form a stable, gel-like substance
in warmer bodies.
When ELPs are injected into a tumor along with radioactive elements, ELPs form a small warehouse that envelops the radioactive atoms
.
In this case, the researchers decided to use iodine-131, a radioactive isotope of iodine, because doctors have used it extensively in medical treatment for decades and its biological effects are well known
.

ELPs warehouses wrap iodine-131 to prevent it from leaking into the body
.
Iodine-131 emits β radiation, which penetrates the biogel and deposits almost all of its energy into the tumor without reaching the
surrounding tissue.
Over time, ELPs degrade into their constituent amino acids and are absorbed by the body – but before that iodine-131 has decayed into a harmless form
of xenon.

Schaal said: "β radiation also improves the stability
of ELPs biogels.
This helps the storage to last longer and only decomposes
when the radiation is exhausted.
”

In the new paper, Schaal and his collaborators in Chilkoti's lab test the synergy of the new therapy with paclitaxel, a commonly used chemotherapy drug, to treat various mouse models
of pancreatic cancer.
They chose pancreatic cancer because of its notoriety for being difficult to treat, hoping to prove that their radiation tumor implants could work synergistically with chemotherapy, while relatively short-lived radiation beam therapy could not
.

The researchers tested their method in mice, where the cancer under the skin was caused
by several different mutations known to occur in pancreatic cancer.
They also tested it on rats with pancreatic tumors, which are more difficult to treat
.

Overall, the test saw a 100 percent response rate in all models, with three-quarters of the models completely eliminating tumors
80 percent of the time.
The tests also showed no immediate and noticeable side effects
other than those caused by the chemotherapy itself.

"We think that constant radiation makes the drug interact with its effects more strongly
than external beam therapy," Schaal said.
"This leads us to think that this approach may actually be more effective
than external beam therapy for many other cancers.
"

However, this approach is still in the early preclinical stage and cannot be used in humans in the
short term.
The researchers say their next step is to conduct large-scale animal trials, where they need to demonstrate that the technology can precisely use existing clinical tools and endoscopic techniques
that doctors have already been trained on.
If successful, they will conduct Phase I human clinical trials
.

Brachytherapy Via a Depot of Biopolymer-Bound 131I Synergizes With Nanoparticle Paclitaxel in Therapy-Resistant Pancreatic Tumours