A research is underway at Flint Animal Cancer Center in Fort Collins that has implications for human head and neck most cancers. Funded by an administrative complement for the Dog Oncology Grant Supplement (DOGS) Program issued by the National Cancer Institute (NCI) from the University of Colorado Cancer Center Head and Neck Cancer Specialized Programs of Research Excellence (SPORE), researchers speculate this research’s findings might enhance outcomes for dogs and people.
Keara Boss, DVM, PhD, CU Cancer Center member and veterinary radiation oncologist at Colorado State University (CSU), is utilizing SPORE funding to review radiation remedy in dogs with sinonasal carcinoma, a sort of head and neck cancer. A subset of the dogs will obtain radiation and a repurposed drug mixture they imagine can optimize the immune system’s response to battle tumors.
A hyperlink between canine and human carcinomas
In people, sinonasal cancers are uncommon, severe, and understudied. Little proof of efficient therapies exist, making this an essential space of research globally. Sinonasal most cancers is linked to occupational publicity resulting from inhalation of commercial and environmental fumes. Unfortunately, restricted efficient, sturdy remedy choices exist for folks identified with sinonasal most cancers.
Boss and her analysis staff have been finding out the shared traits between human and canine cancers by means of a K01 profession improvement award from the National Institutes of Health, with mentorship from CU and CSU school members.
Boss believes finding out naturally occurring canine most cancers can function a mannequin for the human type. Radiation remedy is utilized in each dogs and other people to deal with sinonasal most cancers. Dogs develop sinonasal carcinoma at a better incidence than folks do. Though it’s not recognized why, Boss wonders whether or not, like in folks, it’s associated to what they inhale.
Optimizing the immune system response
Boss says radiation remedy is superb at killing tumor cells, however native tumor recurrence following radiation remedy stays a problem for human and canine sinonasal most cancers sufferers. During the method of tumor irradiation and cell killing, an immune response can be stimulated. This can usher in useful immune cells to each the location that’s been irradiated and all through the physique. But there’s additionally a draw back.
“The flip to that is that radiation can also bring in immune cells that are suppressive to a positive immune response,” Boss says.
She goals to optimize the immune response.
“It’s tricky in cancer. The immune system is doing its best, but tumors hijack the process and trick the immune cells to back off and not fight the cancer.”
She hypothesizes that the introduction of immunotherapy or immunomodulatory drugs will “tip the balance” towards a stimulated immune response by weakening the cells that might in any other case dampen the immune system.
Repurposing blood stress medicines
The research makes use of two blood stress medicines, propranolol and losartan.
Propranolol is a beta blocker that regulates coronary heart fee, blood stress, and blood move. It’s additionally been proven to assist usher in constructive immune cells and “clear out” suppressive immune cells within the tumor microenvironment.
Losartan is an angiotensin receptor blocker that relaxes blood vessels to permit for higher blood move. It has been proven to introduce immune modulatory properties, lowering the power of white blood cells referred to as monocytes to infiltrate tumors. When monocytes enter a tumor, they grow to be macrophages. Macrophages usually dampen constructive immune responses, and losartan has been proven to forestall the suppressive results of monocytes and macrophages inside the tumor and all through the physique.
Losartan may enhance the oxygenation of tumors. Better oxygenation of tumors might permit for a greater response to radiation.
“Radiation alone does crazy things to tumor blood vessels, so we’re thinking the drug combination will help irradiated tumors stay more perfused and may improve responses,” Boss says.
High-dose radiation increases immune response
The study uses stereotactic body radiotherapy (SBRT), a targeted, high-dose intensity administration of energy via X-rays. Traditionally, radiation therapy for head and neck cancer patients uses small, daily doses of radiation given over the course of six weeks, which has not been associated with a robust, positive immune response. This study aims to maximize the immune response and will include three sequential large doses of radiation. The SBRT protocol used for the canine sinonasal cancer patients is similar to SBRT protocols used for human head and neck cancer patients.
The study is examining CT scans before and after radiation, looking at how blood flows to the tumors. The team will compare the differences between tumors treated with radiation alone and tumors treated with radiation and the drug combination.
Boss says having the subset of dogs getting the radiation alone will add to the literature on stereotactic radiation for head and neck cancer. The subset of dogs receiving radiation and the repurposed drug combination adds to the study’s potential in understanding the degree of possible immunomodulation.
“Our hypothesis is that we’ll see improved outcomes with improved immune responses in the dogs treated with the immunomodulatory drug combination,” she says.
A staff effort
The research is funded for one yr, with the potential for extension if wanted. Currently 11 dogs have been enrolled, all of whom had been beforehand identified with most cancers, and funding has been obtained to enroll a further 14 dogs.
Boss credit the significance of the CU Cancer Center staff on this venture, recognizing her colleagues at CSU, Steven Dow, DVM, PhD, and Dan Regan, DVM, PhD. She additionally acknowledges the instrumental position of Sana Karam, MD, PhD, professor of Radiation Oncology on the CU School of Medicine.
“We would have never been given this opportunity had it not been for everyone’s collaboration in making this happen,” Boss says.
This story was revealed by the University of Colorado Cancer Center on September 28, 2023. It is republished with permission.
