In 2022, Jeff Schaal and his colleagues at Duke University in Durham, North Carolina, had a breakthrough in pancreatic cancer research. Claiming to be “the most effective solution yet” for mice models with pancreatic cancer, the new treatment not only stopped tumor growth, but also eliminated malignant tumors in 80 percent of test subjects across several model types, including those classified as the most challenging to treat.
What You Should Know About Pancreatic Cancer
Pancreatic cancer is a highly aggressive disorder resulting from the abnormal growth of cells in the pancreas, a leaf-shaped organ deep within the abdomen. Rapid multiplication or proliferation of cancer cells in the organ’s tissues characterize this life-threatening disease. It often spreads to both neighboring and distant sites in the body, especially in the abdominal cavity, liver, and lungs.
1. Asymptomatic in Early Stages
Pancreatic cancer is notorious for its stealthy nature. In most cases, it remains asymptomatic, making early detection and treatment difficult. As pancreatic cancer progresses, symptoms such as sudden and unexplained weight loss, abdominal pain, jaundice, and digestive issues may arise.
2. Fatal in Advanced Stages
Because pancreatic cancer conceals its symptoms until later on, it is frequently diagnosed at an advanced stage, limiting treatment options and resulting in a low survival rate. Approximately 95 percent of patients succumb to it, CNN Health disclosed.
Related: Addressing the Challenges of Treating Pancreatic Cancer
Despite advancements in clinical research and therapies, pancreatic cancer continues to pose a formidable challenge to patients and healthcare providers worldwide. In hindsight, the discovery of a new treatment may improve overall survival rates and prognoses.
3. Resistant to Many Drugs
Pancreatic cancer is the third leading cause of cancer-related deaths but accounts for only 3.2 percent of all cancer cases. In 2023, an estimated 64,050 people in the United States will have pancreatic cancer, and as many as 50,550 of them will die from the disease.
These tumors typically have aggressive, drug-resistant genetic mutations. Moreover, many individuals do not seek medical intervention until symptoms manifest, which often signals that cancer is already in an advanced stage.
Case Study: Radioactive Tumor Implant for Pancreatic Cancer
The approach by Duke University’s biomedical engineers integrates conventional chemotherapy drugs with a new technique for irradiating the tumor (radiation therapy). It involves implanting radioactive iodine-131 inside the tumor via a gel-like capsule, which safeguards normal tissue and is broken down by the body once the radiation fades. Traditionally, radiation therapy from an external beam impacts healthy tissue, causing side effects such as infertility, hormone deficiencies, and secondary cancers. This new and revolutionary approach prevents such side effects.
“We did a deep dive through over 1100 treatments across preclinical models and never found results where the tumors shrank away and disappeared like ours did,” shared Jeff Schaal. He conducted this research during his Ph.D. in the Ashutosh Chilkoti laboratory, the Alan L. Kaganov Distinguished Professor of Biomedical Engineering at Duke University.
Initial Challenges
The researchers combined chemotherapy, which makes proliferating cancer cells vulnerable to radiation exposure, with a radiation beam directed at the malignant growth. However, this approach proved ineffective until a specific level of radiation reaches the tumor. The researchers also faced the following setbacks:
1. Radiation Compromises Healthy Tissue
Despite recent advances in external radiation shaping and targeting, reaching a tumor without affecting normal tissue and causing side effects remain challenging.
2. Titanium Blocks Radiation
Early on, the researchers attempted to implant a radioactive sample encased in titanium into the tumor. However, they found that titanium inhibited all radiation apart from gamma rays, which traveled far outside the malignant growth and could only remain inside the body for a brief period before inflicting damage to surrounding tissue, defeating the study’s overall purpose.
Breakthrough With Elastin-Like Polypeptides
Learning from the above issues and making improvements, Schaal experimented with another implantation technique using a material made from elastin-like polypeptides (ELPs).
ELPs are biopolymers inspired by elastin, an essential protein providing elasticity and resilience to tissues, enabling them to stretch and recoil. Elastin-like polypeptides consist of repetitive amino acid sequences, often derived from the primary sequence of elastin. They are bonded together to produce a gel-like substance with customized properties.
According to Schaal, the Chilkoti lab specializes in ELPs, so he was able to collaborate with his colleagues to devise a drug delivery system appropriate for the task.
Understanding Injectable ELP Depots for Drug Delivery
ELPs have a liquid form at room temperature and produce a gel-like material inside the human body. In pancreatic cancer, when an authorized individual injects ELPs in a tumor along with radioactive iodine-131, the self-stabilizing biopolymers structurize a depot encasing radioactive atoms. For decades, medical professionals have been using iodine-131 to treat various health issues, including hyperthyroidism and thyroid cancer, due to its biological effects.
The injectable ELP depot holds the iodine-131, ensuring it does not leak and discharge into the body. This radioisotope of iodine emits beta radiation, which can penetrate through the gel and release nearly all of its energy into the malignant tumor without impacting the surrounding tissue. Eventually, the ELP depot will break down into its amino acid parts, allowing the body to absorb it.
“The beta radiation also improves the stability of the ELP bio gel,” shared Schaal, currently director of research at Cereius Inc., a biotechnology startup in Durham, North Carolina. “That helps the depot last longer and only break down after the radiation is spent.”
Primary Test Subjects
Schaal and his colleagues tested their drug delivery system on rodents with malignancies under the skin, which formed through different mutations known to arise in pancreatic cancer. They also examined the method’s effects on mice with pancreatic tumors, which are significantly more exhaustive to treat.
Results
The results demonstrated a 100 percent response rate across all test subjects, with the tumors regressing in three-quarters of the mice about 80 percent of the time. Furthermore, except for chemotherapy’s side effects, the new drug delivery system did not cause any adverse effects.
Keep in mind, however, that the approach is in its preclinical stages and will not be available for human cancer patients in the near future. Schaal says they intend to conduct larger animal trials, where he and his team can determine whether the technique can work alongside existing clinical tools and techniques. If successful, they may proceed with a clinical trial focused on humans.
“My lab has been working on developing new cancer treatments for close to 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 and is invariably fatal,” Chilkoti revealed. “Pancreatic cancer patients deserve better treatment options than are currently available, and I am deeply committed to taking this all the way into the clinic.”
Sources:
- Gel-Like, Radioactive Implant Obliterates Pancreatic Cancer in Mice. (2022, October 21). Duke Pratt School of Engineering. https://pratt.duke.edu/about/news/radioactive-tumor-implant
- Injectable ELP Depots for Drug Delivery | Chilkoti Group. (n.d.). http://chilkotilab.pratt.duke.edu/research/project/injectable-elp-depots-drug-delivery
