First clinical trial in cats tests targeted therapy for deadly head and neck cancer

Researchers have reported results from the first-ever clinical trial of a new class of targeted therapy in pet cats with head and neck squamous cell carcinoma (HNSCC)-a cancer which is notoriously deadly and difficult to treat. Publishing in the Cell Press journal Cancer Cell on August 28, the study found that 35% of the cats who received treatment had their disease controlled with minimal side effects-and the drug will likely be effective for humans with HNSCC as well. 

There are two major findings from this study. It showed us that it's possible to target a transcription factor that drives oncogenesis, which is something that has been notoriously difficult in the past. Also, it demonstrated that pets with cancer can be a good representation of human disease and that clinical trials in pets may yield more reliable results than tests in mouse models." 

Daniel Johnson, senior author of the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center

This drug, which was initially conceptualized to treat human head and neck cancers, is the first to target the transcription factor STAT3. STAT3 is present in a range of both solid and liquid tumors, including a majority of HNSCC cases. 

The idea to test the HNSCC drug on pet cats came from a discussion first author Jennifer Grandis had with her sister, a veterinarian. Grandis learned that oral cancers like HNSCC in pet cats are extremely difficult to treat and that most animals die within 2 to 3 months of diagnosis. 

"There is remarkable clinical, histopathologic, and immunologic similarity between feline and human HNSCC," the authors write. 

One cat who benefited from the trial was a 9-year-old black domestic shorthair named Jak. When he was diagnosed with HNSCC, the veterinarian gave him only 6 to 8 weeks to live. 

"It was just a gut punch," says his owner, Tina Thomas. "We wanted more time with him. When I found out about this clinical trial, I knew I wanted him to be a part of it." 

Jak went for weekly treatments for one month. During that time his symptoms-mainly, a watery eye-greatly improved. He ultimately lived more than 8 months after his diagnosis. 

"It was meaningful to us because he was here in our lives," says Thomas. "During that time, my son finished college and my daughter finished her master's program. Jak got to spend one more Christmas with us, and he loved our Christmas tree. He was worth every bit of the effort." 

Other than mild anemia, none of the cats in the trial developed side effects that were attributable to the treatment. Of the 20 cats that were enrolled, 7 of them exhibited either a partial response or stable disease during the study period. Among the 7 that responded, the average survival post-treatment was 161 days. 

When the investigators looked at tumors and blood samples from the cats who underwent treatment, they saw that the compound was working in two ways: It not only blocked the activity of STAT3 but it also raised levels of PD-1, a protein associated with an immune response to cancer. 

"This study is a great example of how we can think more carefully about spending our very limited resources on studies in lab mice that are not even the best models of human cancers," Grandis says. "By partnering with veterinary oncologists and doing clinical trials in companion animals, we can learn an enormous amount about how these drugs work while also helping people's pets. None of the cats in these trials were harmed, and many of them benefited." 

The researchers say that conducting clinical trials in pets can be a much better model of how drugs will work in humans compared with lab mice. They are currently working with a small biotech company to advance the new compound in clinical trials for both pets and humans. 

"These animals breathe the same air that we breathe and are exposed to all the things we're exposed to," says Johnson. "Their tumors are much more heterogeneous, which makes them a better mimic of human disease."