A clinical trial involving pet cats with naturally occurring head and neck squamous cell carcinoma has produced promising early results for a therapeutic agent targeting the STAT3 transcription factor. The work involved a cross-disciplinary collaboration spanning human cancer research and veterinary oncology in United States academic institutions.
Experimental STAT3 Therapy in Pet Cats Shows Early Promise for Human Head and Neck Cancers in Phase One Trial Results
The findings show how veterinary patients with naturally occurring tumors can accelerate drug development, help researchers validate mechanisms, and generate clinical insight before advancing into human oncology settings.
Background
Head and neck squamous cell carcinoma in cats is an aggressive malignancy that typically allows only two or three months of survival after diagnosis. Veterinary oncologists have further reported that conventional treatments like surgery, radiation, and chemotherapy seldom provide durable control of tumors in the oral cavity or surrounding tissues.
Investigators led by Daniel Johnson and Jennifer Grandis developed a cyclic oligonucleotide decoy aimed at blocking Signal Transducer and Activator of Transcription 3 activity. They recognized that this is a similar signaling that drives tumor progression in human and feline cancers and sought a translational model beyond conventional mouse experiments.
A phase one trial was organized with the help of the Davis School of Veterinary Medicine. There were 20 pet cats with confirmed oral or head and neck squamous cell carcinoma selected to receive weekly administrations of a particular STAT3 decoy. These cats were monitored for chemistry, tumor response, and molecular biomarkers throughout the trial.
Key Findings
The trial demonstrated several clinical outcomes that addressed safety, tolerability, biological engagement, and potential survival advantages. Investigators documented both quantitative tumor responses and laboratory evidence that the therapeutic agent interfered with its intended molecular pathway while causing limited adverse effects in the enrolled animals.
• Notable Safety Profile
Mild anemia was the only consistent adverse effect reported, and no dose-limiting toxicities were observed across the participating subjects during the treatment period.
• Particular Tumor Response
7 of the 20 cats showed either partial response or stable disease. Responders experienced an average survival duration of 161 days. This exceeded the typical prognosis.
• Molecular Target Engagement
Biopsies confirmed reduced STAT3 signaling within tumors. This indicates that the cyclic decoy reached and inhibited its intended intracellular pathway in live subjects.
• Immunological Indicators
Increased PD-1 expression in blood samples suggested potential activation of immune mechanisms that could augment the direct antitumor effect of the agent.
• Illustrative Case Outcome
One 9-year-old cat named Jak, initially given a 6 to 8 week prognosis, received 4 weekly treatments and survived more than 8 months with improved daily function.
Implications
Note that the favorable safety record encourages continued development of strategies centered on targeting transcription factors across veterinary and human oncology practices. Mild anemia represented the only consistent adverse finding and did not require cessation of therapy, alteration of schedules, or substantial dose reduction in the participating animals.
The demonstration of STAT3 inhibition in tumor tissues supports the hypothesis that cyclic decoy molecules can reach intracellular targets previously regarded as inaccessible or impractical. The observed increase in PD-1 expression suggests that immune pathways via programmed cell death may cooperate with the agent in limiting malignant progression.
Results of the phase one trial provide an evidence base for targeting a pathway that also drives progression in human head and neck squamous cell carcinoma. The trial demonstrated that a cyclic oligonucleotide decoy can penetrate tumor tissues, disrupt a transcription factor traditionally considered undruggable, and produce measurable biological effects.
The observations above provide early confirmation that similar mechanisms could be exploited in human malignancies where the STAT3 protein also influences tumor survival, angiogenesis, and resistance to therapy. The immunomodulatory potential of STAT3 inhibition may also support combination strategies with checkpoint inhibitors in human cancer patients.
FURTHER READING AND REFERENCE
- Grandis, J. R., Skorupski, K. A., Cheng, N., Cui, Z., Li, H., Woerner, L. C., Gencel-Augusto, J., Zeng, Y., Shiah, J. V., Bhola, N. E., Sen, M., Blum, K., Kim, M.-O., York, D., Rebhun, R. B., Chang, H., Murad, N. F., Olshen, A. B., Sparger, E. E., and Johnson, D. E. 2025. “Safety and Efficacy of a STAT3-Targeted Cyclic Oligonucleotide: From Murine Models to a Phase 1 Clinical Trial in Pet Cats with Oral Cancer.” Cancer Cell. DOI: 1016/j.ccell.2025.07.015