Unlocking the Secrets of Cell Death in Dogs: A Pathway to Future Therapies
Every moment, cells in both your body and your dog’s are reaching the end of their life cycle. Understanding how they die could unlock new therapies for cancer and autoimmune diseases. But not all cell deaths are the same. Cells can die accidentally or follow a built-in safety program called programmed cell death, a process that helps maintain health by removing damaged or stressed cells.
This research helps us understand how evolution shaped programmed cell death to regulate immune responses in different species, says Workenhe. By learning from dogs, we can design therapies that improve health for both animals and humans.
OVC provides unique opportunities to take discoveries made in cell lines into medicines that can benefit companion animals and humans. These findings help us think about relevance from both perspectives.
Sometimes, cell death happens in a controlled, tidy way. Cells break down into small pieces that are quickly cleared by other cells. This process, called apoptosis, is essential for normal developmental functions like replacing old skin cells. Other times, cells die explosively, bursting apart and releasing chemical signals that trigger inflammation and alert the immune system the presence of danger. One type of this dramatic cell death is known as necroptosis. Necroptosis often occurs during infections or cancer treatment.
Both forms of programmed cell death are vital for health, but dogs are different. They lack a key gene, MLKL, which is necessary for necroptosis in humans and mice. Necroptosis acts like an alarm system: when a cell bursts apart, it releases danger signals that rally the immune system to fight infections or destroy cancer cells. Without this pathway, dogs lose that dramatic “call to arms.” Instead, their cells rely on apoptosis, a quieter, cleaner process that doesn’t trigger the same level of immune activation.
This difference matters because it changes how dogs fight disease. In humans, necroptosis helps clear viruses and attack tumors by creating inflammation that mobilizes immune defenses. In dogs, the absence of necroptosis might make them more vulnerable to certain infections or allow cancers to grow without as much immune resistance. On the other hand, it could protect dogs from excessive inflammation, which in humans can lead to autoimmune diseases. Understanding this trade-off is key to designing therapies that either boost immune signals when fighting cancer or dampen them when treating inflammatory conditions.
Sarah Worfolk, the PhD student leading the study, recently published in Springer Nature, explains: “It’s fascinating because this isn’t just about dogs, it’s about evolution. Dogs seem to have adapted to avoid the inflammatory chaos that necroptosis brings, but that comes at a cost. Our research is about figuring out how to work with that difference to improve treatments for both species.”
She discovered that when a typical necroptosis trigger is introduced, the dog cells die by an unusual kind of apoptosis. “It’s a more immunogenic version,” says Worfolk, “meaning it still sends signals to the immune system. That was a big surprise.”
To make sense of it, she offers an analogy: “In humans, necroptosis is like a blaring car alarm, loud and inflammatory. In dogs, it’s more like a quiet text alert. The message still gets through, but without the chaos.”
Why does this matter? The implications are vast. In cancer, tumours often suppress immune responses, allowing them to grow unchecked. Harnessing immunogenic apoptosis could help stimulate anti-tumour immunity, making treatments more effective. Conversely, in autoimmune diseases where the immune system is overactive, targeting these pathways could reduce harmful inflammation. The research also opens doors to refining chemotherapy by identifying treatments that trigger the most beneficial form of cell death.
Noah Phippen, a Research Associate and lab manager, as well as a contributing author in this study, highlights the next steps: “We want to see if this pathway behaves the same way in different tissues and in cancer cell lines. The OVC Veterinary Biobank contains thousands of samples of canine tumours, which gives us a unique opportunity to test this in real-world disease contexts.”
Beyond cancer, the findings could influence treatments for viral infections and chronic inflammatory conditions. By mapping how cell death pathways differ between species, scientists can fine-tune immune responses, either amplifying them to fight cancer or dampening them to treat autoimmune disorders.
This study was funded by OVC Pet Trust, whose support enables discoveries that benefit pets and people alike.
