Canine hemangiosarcoma study aims to identify personalized treatment options

In a recent article published in Nature, researchers evaluated spontaneously arising canine splenic hemangiosarcoma (HSA) samples for genetic biomarkers that correlated with their response to various treatment options. The study aimed to identify new ways to personalize treatment options for both canine splenic HSA and the histologically and genetically similar (but much more rare) human angiosarcoma using genetic testing of tumor cells and comparison of responses to adjunctive chemotherapy and small molecule targeted therapy options.  

Lucas Rodrigues, DVM, MS, PhD, Head of Veterinary Research at FidoCure, was lead author on the study. “This real-world study highlights the effectiveness of two small molecule targeted therapies when they are included as a component of a targeted therapy approach,” he said. “Our data suggests patterns of genetic mutation can be used to identify specific subgroups and biomarkers,” he added, which may help determine why traditional chemotherapy protocols so often fail in the treatment of canine hemangiosarcoma.  

Canine hemangiosarcoma  

Rachel Venable, DVM, MS, DACVIM (Oncology), CEO of Pet Cancer Care Consulting (who was not involved in this research study), described visceral hemangiosarcoma as “very aggressive” with one-year survival rates of less than ten percent, even with surgery and chemotherapy. “At this point,” she added, “I am open to most options for this cancer because it is so aggressive and we have not had much success treating it.”

In an effort to find new and more effective treatment options for patients diagnosed with this aggressive neoplasm, researchers all over the world have been actively studying the disease. Studies have included clinical trials that evaluate human chemotherapy drugs, a vaccine for dogs with splenic hemangiosarcoma, and a group of eight studies funded by the Morris Animal Foundation covering everything from new detection techniques to novel chemotherapy delivery methods.  

Rodrigues’ team is one of several research teams focusing on the genetic differences between HSA cells in individual dogs. He said that knowing each dog’s unique cancer profile allows veterinarians to personalize their treatment recommendations.  This cancer profile includes their tumor’s unique genetic mutations, such as the PTEN and TP53 tumor suppressor mutations and the ATRX mutation.  

About the study 

Samples were obtained from 508 dogs who had undergone splenectomies, been diagnosed with HSA, and enrolled in FidoCure, a platform that uses genetic testing to identify tumor-specific mutations to recommend personalized treatment options. The FidoCure panel screened for mutations in 48 different “cancer genes”—genes that would normally prevent abnormal cell growth—in total.   

Dogs in this retrospective study were placed into one of four groups based on the treatment they received: splenectomy alone, splenectomy with adjuvant chemotherapy, splenectomy with small molecule targeted therapy, and splenectomy with both chemotherapy and small molecule targeted therapy.  

Small molecule targeted therapy is defined as the use of small molecule drugs (less than 500-1000 Daltons) that can enter cells easily due to their size and that target pathways inside cells that are more specific to cancer cells. The goals of this type of therapy include improved efficacy against cancer cells and reduced side effects when compared to adjuvant chemotherapy treatment. These drugs are usually administered orally.  

The small molecule therapies evaluated in this study included rapamycin, a mammalian target of rapamycin (mTOR) inhibitor; vorinostat, a histone deacetylase (HDAC) inhibitor; and trametinib, a selective mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor. Rapamycin is labeled as an immunosuppressant drug for humans and is being actively studied for its potential as a longevity drug in dogs. It is of interest as an anti-cancer drug for both humans and dogs because of its ability to slow proliferation of rapidly dividing cells. Vorinostat and trametinib are both used to treat various types of neoplasia in humans.  

Study results 

Results of this study indicated that dogs receiving both small molecule targeted therapy and chemotherapy after surgery survived on average 211 days, longer than dogs who had only surgery (81 days) and dogs who had either chemotherapy or targeted therapy (but not both) after surgery (140 days and 149 days, respectively). 

Treatments aside, variables impacting survival time included the stage of the tumors and the specific cancer gene mutations found in each tumor.  “Our data analysis identified that mutations in PTEN and TP53 genes are associated with poor outcome in dogs with splenic hemangiosarcoma,” Rodrigues said. Dogs who had either or both mutations had survival times that were 63 to 75 days shorter than those without these mutations.  

The poor outcomes associated with the TP53 mutation are a significant area of interest, Rodrigues explained, because this mutation is found in 40 to 60% of canine splenic HSA samples. Patients in this study who were found to have the TP53 mutation had longer survival times when rapamycin and/or vorinostat were included in their treatment regimen. Trametinib did not appear to increase survival times in these cases.  

Venable found the results of this study to be “encouraging,” citing a twenty percent one-year survival rate when targeted therapies were used in addition to surgery and chemotherapy. “As we do more research into treating cancer, we are finding that multiple different types of treatments are needed to kill tumor cells and get better results. This study also showed that a one-size-fits-all does not work with targeted therapies and the best results really depend on the mutations present,” she said.

The value of precision medicine 

Precision medicine, or the tailoring of a treatment plan around a patient’s genetic makeup, environment, and lifestyle, appears to be an important element in determining the most effective therapies for aggressive cancers like HSA going forward.  

“As precision medicine becomes more feasible in veterinary settings, understanding how specific genomic alterations influence prognosis and treatment response, even outside of controlled clinical trials, can help guide more individualized and evidence-based care for patients,” Rodrigues said. 

He also highlighted that the use of small-molecule targeted therapies may also improve access to care for some families. “Because these targeted therapies are oral and easily administered, they are more accessible to general practitioners, not just oncologists, which can expand care options for clients who might otherwise decline treatment due to limited specialist access or cost constraints,” he said.  How accessible these therapies end up being will also depend on the retail cost of the drugs, some of which are currently thousands to tens of thousands of dollars for thirty-day supplies.

Venable added that genetic testing and targeted therapy are often hotly debated among oncologists due to a relative lack of data on safety, efficacy, and dosing of many of the targeted therapy drugs in comparison to what is known about their use in humans. “Until we have the data showing how the different tumor mutations affect survival time and treatment outcome with the specific targeted therapy including effective dose and side effects, there will be arguments and concerns with this technology,” she explained.

Therefore, continued research by FidoCure and others to find effective and accessible therapeutic options is essential to changing the prognosis for dogs diagnosed with this deadly disease.

“It is an exciting time in medicine,” Venable said, “but also a difficult one.”

Further reading: 

Real-world evidence couples genomic biomarkers with therapeutic outcomes for canine hemangiosarcoma 

Exploring new treatment options for a devastating cancer 

The Morris Animal Foundation’s 75-year legacy of pioneering research 

Palliative care: The missing piece of chronic disease management 

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives 

Photo credit: Bigandt_Photography/iStock via Getty Images 

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