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What's New With Canine Hemangiosarcoma?

a jack russel dog sits on crumchy leaves

In a section of the Small Animal Clinical Oncology textbook re-edited in 2020, a chart shows a compilation of studies and treatments used in dogs after splenectomy. Median survival times with only splenectomy were between 19 and 86 days. With doxorubicin-based chemotherapy, the survival bettered to 172 to 210, and the long list of combinations remained within the same range. Three combinations showed a significant increase in days, so they analyzed them. 

The first one was a protocol of splenectomy, doxorubicin, and dacarbazine, another chemotherapy drug. The median time jumped to 550 days, but researcher Dr. Laura Marconato expressed that having the dogs go through this very aggressive treatment for extra survival time was not beneficial. Weighing the side effects and quality of life is necessary when considering a combination chemotherapy. 

The second was splenectomy and doxorubicin with muramyl tripeptide immunotherapy, with a median survival of 277 days. This synthetic drug enhances chemotherapy by killing harmful cells more efficiently. The study from the 90s is outdated for current reference, and the drug, while used for pediatric cancer treatment, is not approved for veterinary use. 

The last promising combination is Ebat, currently tested and developed at the University of Minnesota, giving 258 median survival time. Ebat targets EGF receptors and delivers a toxin to the cancer cells. Data is starting to be released, and according to the webinar, a private institution is planning to launch the combination in the market by the end of this year.

In tackling the elusive ways of canine hemangiosarcoma, the research explores every possible angle to shed light on. One focus nowadays is targeting the cells surrounding the tumor instead of having treatment attack exclusively cancer cells. Tumor cells can attract and modify cells around them to be immune-suppressive and block the T-cells from reaching cancer cells. The webinar spoke about one study from Colorado State University that is in the early stages of focusing on a classification of these cells called fibroblasts, which FAK Inhibitors can interfere with to prevent migration of cancer cells and metastasis. They expect to share some early results by this summer to see if this strategy can make a difference. 

Another surprising finding by researcher Elizabeth Rapatasky was around two groups of mice. In one group, cancer grew much faster than the other, despite all the conditions being the same except for one: the temperature in the rooms was significantly lower where the mice with fast-growing cancer inhabited. This cold-induced stress triggered additional research to observe how sympathetic nerves generate stress molecules that feed the cancer cells and suppress the immune system. She decided to introduce propranolol, an oral beta blocker used for hypertension known for having anti-cancer properties as well, to suppress this mechanism and stop tumor growth. 

During this year at the World Veterinary Cancer Congress, researcher S.Salgado and his team exhibited 29 cases of retrospective patients who were treated with splenectomy, doxorubicin, and propranolol and saw that for patients visceral hemangiosarcoma median survival time jumped to 471 days. When asking veterinary professionals about the use of propranolol when treating dogs, some use it regularly as they feel the benefits are tangible, and others don't see much of a point. The University of Minnesota is currently performing a study on propranolol that has just finished enrolling.  

Immunotherapy - designed to utilize antibodies and white blood cells of the immune system to attack tumor cells - is revamping oncology with checkpoint inhibitors, which help the immune system fight cancer cells that try to deactivate it. Early results of a study on the EGFR/Her2 vaccine were presented at the congress. It was performed on 39 diagnosed dogs, resulting in a median survival for dogs with surgery, chemotherapy, and the added vaccine of 268 days. The pharmaceutical company MercK has recently introduced Gilvetmab, the first immune checkpoint inhibitor drug currently aimed at dogs with mast cell tumors and melanoma. The foundation is currently supporting a study that combines the EGFR/HER2 vaccine with chemotherapy and Gilvetmap. The goal is to determine if blocking two specific checkpoints and preventing cancer from disabling the immune system will improve the vaccine's performance. 

As stated by Kaplan-Meier curves, the earlier the diagnosis, the higher the chance of survival. Diagnosing stage I (unruptured spleen/tumor) means the best scenario for dogs, which is why so many cancer tests analyzing blood, urine, and saliva, looking at cell-free DA, chemotaxis, and even canine scent detection with worms, are motivated to reach the market with the mission of detecting it before reaching an emergency state. Dr. Heather Wilson-Robles, one of the creators of the Nu.Q test, explained at the Veterinary Cancer Meeting how monitoring a patient before and after splenectomy and following chemotherapy taught them how nucleosome levels fluctuate in the different stages, giving close monitoring technologies a prospect at getting sharper. Another test by a company in Maryland that is still not commercialized is analyzing blood screenings from cancer-positive samples associated with particularly large macrophage cells, indicating cancer cells had eaten them or fused with them. This new observation could lead to better diagnosis since these large cells are mostly found in canines that don't respond well to treatment. All these innovations in diagnosis may enable that when sampling of tumors or biopsies is a dangerous option, a simple, less-invasive test could be sufficient to see the shifts in the disease. 

The Canine Cancer Alliance is a volunteer-driven association focused on informing and funding research to eradicate canine cancer and improve treatments. This video is the first of a promising series of webinars that will discuss the latest about Hemangiosarcoma, which luckily keeps being discovered through research, studies, and early deduction, aiming at improving diagnosis and treatments for dogs with this type of cancer. If you are interested in watching the full webinar, you can click here.


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