The first-ever clinical trial of a new targeted therapy for head and neck squamous cell carcinoma (HNSCC) has found promising results in pet cats, with the disease controlled in 35% of the animals that received the treatment.
The team behind the research is hopeful that the drug will also be an effective treatment for humans with the disease.
The results are published in a paper in the journal Cancer Cell.
HNSCC refers to a group of head and neck cancers that originate in squamous cells in the mouth, throat or nasal cavity. These cancers can cause a wide range of symptoms such as nausea, nerve damage and inflammation of the mouth, and can be difficult to treat.
In 2020, there were 1,177 deaths from head and neck cancer in Australia, with an estimated 5,189 new cases diagnosed in 2022.
The novel drug was initially intended to treat human cancers by targeting the transcription factor STAT3. The drug is the first to target STAT3, a protein that promotes tumour growth in many HNSCC cases.
Typically, in the medical field, new therapies will be tested on mice in a lab before clinical trials for humans. The team opted to test the drug on domestic cats instead.
The idea came from first author Jennifer Grandis, who was talking to her veterinarian sister about oral cancers in pet cats. Cases of HNSCC in felines are very challenging to treat and most animals die within 2 to 3 months of diagnosis.
“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,” says Grandis, who is a professor at the University of California, San Francisco (UCSF) in the US.
The research team gave the experimental drug to 20 pet cats with HNSCC. Apart from mild anaemia, none of the cats in the trial developed side effects from the treatment. No cats were harmed in the trial.
They found that 7 of the cats either stabilised or partially responded to the treatment and survived for an average of 161 days post-treatment.
Blood samples and tumour scans revealed the new therapy worked by not only blocking STAT3 activity, but also raising levels of PD-1, a protein linked to an immune response to cancer.
“There are 2 major findings from this study,” says senior author and UCSF Professor Daniel Johnson.
“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.”
The second finding is one that the researchers hope has the most promising implications for humans.
“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.”
The results highlight the strong similarities between feline and human head and neck cancer development. In both cats and humans, HNSCCs are naturally occurring and share similar expression of and mutations in key biomarkers.
“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,” says Grandis.
“These animals breathe the same air that we breathe and are exposed to all the things we’re exposed to,” adds Johnson.
“Their tumours are much more heterogeneous, which makes them a better mimic of human disease.”
One of the cats that underwent the study was Jak, a 9-year-old black domestic shorthair.
“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,” says Tina Thomas, Jak’s owner who had originally been told he only had 6 to 8 weeks to live.
After receiving weekly treatments for 1 month, Jak lived for another 8 months after his diagnosis.
“It was meaningful to us because he was here in our lives,” says Thomas.
The researchers are working with a small biotech company to get clinical trials running for this new drug in both pets and eventually humans.