While many scientists at the Flint Animal Cancer Center focus their research on cancer cells, the Laboratory of Comparative Musculoskeletal Oncology and Traumatology views cancer through an additional lens.
“Many of our colleagues are doing great work focusing on cancer itself – how to treat it effectively, how to make sure it doesn’t spread,” said Dr. Nicole Ehrhart, lab director and surgical oncologist. “The other side of that coin is anything that we do that treats cancer, whether that’s chemotherapy or surgery or radiation also has effects. It’s important that we work on both sides of the coin.”
The goal of cancer surgery is to completely remove the cancerous tumor, sometimes that requires limb amputation. Other times, it involves the removal of large amounts of muscle tissue. However, the impact of cancer surgery can continue for years beyond the last treatment. Unfortunately, many patients, animals and humans, face complications down the road, including infection, non-healing surgical incisions, and loss of muscle function.
“Our laboratory focuses on how, following a successful surgery, we can minimize surgical complications, reduce healing time, and improve quality of life,” said Dr. Ruth Rose, assistant lab director and surgical oncologist.
One area of study focuses on restoring muscle function using stem cells.
Stem cells exist in every tissue of the body and are essential in healing, but they can only do so much naturally. About ten years ago, Dr. Ehrhart wondered if it would be possible to boost the body’s regenerative response.
“When a large section of muscle has to be removed, the body can’t regenerate enough tissue to function well,” said Ehrhart. “We wondered if we could regenerate muscle by removing the cells from donor tissue and using the patient’s own stem cells to regenerate the muscle into functional tissue. In our laboratory studies, we’ve found that yes, we can regenerate muscle in a way that really helped preserve function.”
Most recently, they learned that exosomes, tiny particles released from stem cells, produce the same results, with fewer limitations, which allows them to scale up in a way they would not be able to do with the cells. As a result, Ehrhart sees exosomes as the next generation of their stem cell work.
Rose is also exploring the healing powers of exosomes as a possible solution to prevent postoperative infection.
Infection is a common complication following cancer surgery and can impact patient quality of life and delay healing, which may interrupt additional treatments like chemotherapy or radiation therapy. Rose is studying whether exosomes can tell the body to prepare to fight infection to address the issue.
So far, they’ve seen a reduction in localized infection in laboratory models. Their work will continue with the hope of bringing the treatment to patients.
“We think this treatment has the potential to shorten healing time and also reduce complications over time,” said Rose. “I truly believe everything that we do is going to help our patients at the animal cancer center, but I believe it’s going to help people as well.”
Overcoming obstacles in measuring radiation dose delivery
By profession, Dr. Del Leary is a medical physicist. In practice, he’s a problem-solver.
“I really like solving problems and thinking outside of the box,” said Leary. “I’m lucky I get to do that just about every day in my job.”
As a medical physicist, Leary is concerned with monitoring the therapeutic index, which is the amount of radiation delivered to the tumor divided by the amount of dose to normal tissue.
Calculating the therapeutic index is relatively easy when treating patients using the linear accelerator, which delivers radiation evenly regardless of the material (bone, tissue, air) it passes through. However, a different technology, called a small animal irradiator, uses lower energy photons to target tumors. This lower energy radiation is atomic number dependent, which means bone absorbs the radiation at much higher rates than the soft tissue.
The Flint Animal Cancer Center recently started treating companion animals such as ferrets, birds, and guinea pigs using a small animal irradiator. The technology provides a therapeutic option previously unavailable for these patients due to their size.
Leary’s challenge using the small animal irradiator was measuring the dosage to calculate the therapeutic index accurately.
“It’s important to know if the tumor that’s behind the scapula absorbed the prescribed dose,” said Amber Prebble, radiation oncology technician, graduate student in radiation cancer biology, and physics lab manager.
Digging into the problem, Leary, with the help of Prebble and Dr. Erin Trageser, radiation oncology resident, has devised a two-step approach.
The first step uses 3-D printing technology to create anatomically accurate patient models, also called phantoms. In designing the phantoms, they worked to identify materials that replicate the atomic numbers of bone, tissue, and even lungs. The purpose of the models is to help verify dose delivery.
“The models are helpful, but we were still missing a tool, a good dosimeter, to help us accurately measure dose delivery,” said Leary.
That’s where Dr. Erin Trageser’s project fits in. Under the supervision of Leary, Trageser is developing a gel dosimeter.
The gel uses gold nanoparticles, and when the concentrations are right, they react with radiation, which changes their molecular composition and, as a result, changes their color. The color changes will allow the team to establish a calibration curve to understand the amount of dose delivered to the tumor and surrounding tissues.
“As a gel, it can fill in anywhere and form to any curvature,” said Leary. “It’s still a bit of a work in progress, but we believe we can get there and have full three-dimensional information regarding where the radiation was delivered.”
In addition to accurately measuring dose delivery, the gel dosimeter might provide another benefit.
“We think the nanoparticle technology could potentially increase the dose locally to tumors, which could give us better tumor control and better survival times for cancer patients, not only for animals but people as well,” said Trageser.
“I think the gel dosimeter is going to be the perfect tool to use with our 3-D printed phantoms,” said Leary. I’m excited to see how this comes together – to test, verify, and ultimately use to treat patients.”
LEADERS IN COMPARATIVE ONCOLOGY RESEARCH
For nearly four decades, the Flint Animal Cancer Center has been at the forefront of understanding the fundamental mechanisms of cancer biology, disease diagnosis, and the development of effective therapies. Our comparative oncology research program houses ten laboratories, 14 areas of research and includes 50+ team members, all on a mission to conquer cancer in all species.
We invite you to partner with us in our journey to answer the fundamental questions that will lead to cancer breakthroughs for pets and people. Please consider a gift to our basic science research program today. Your support provides the funding we need to continue to ask critical questions and chase down the answers. To learn more about this opportunity, please email Torii Kapavik, development director.