Like many of the owners who wind up in the Clinical Trials Office at Cummings Veterinary Medical Center, Mary Elizabeth Titmas seemed to vacillate between worry and hope.
About a year ago, Titmas and her husband noticed a bump on the front leg of Ellie, their 11-year-old boxer mix. But over the last couple of months, that walnut-size lump had grown to the size of a grapefruit. A biopsy delivered the crushing diagnosis of soft-tissue sarcoma, a cancer that often grows too quickly to be surgically removed and tends to resist chemotherapy and radiation. Since Ellie still seemed to enjoy good quality of life, the couple wanted more time with her, but they were unsure about their options. Would surgeons have to amputate Ellie’s leg to remove the tumor? Was surgery even possible?
Then, in May, Titmas stumbled upon a cover story in the Boston Globe’s Sunday magazine about Cheryl London, V90, a veterinary oncologist at Tufts and director of the Clinical Trials Office. As the newly appointed Anne Engen and Dusty Professor in Comparative Oncology, a professorship supported by donors Anne and Travis Engen in honor of their late dog Dusty, London studies new cancer therapies being developed for humans in pets being treated for similar cancers. Two of the dogs featured in the magazine story had their soft-tissue sarcomas dramatically shrink after receiving an experimental therapy in a clinical trial.
Titmas called London’s Clinical Trials Office and, by late July, she was meeting with clinical-trials technician Michelle Willette and veterinary clinical-trials intern Alyssa Przydrozny to discuss the study. Developed by Cambridge, Massachusetts-based biotech Jounce Therapeutics, the immunotherapy approach seeks to enlist the patient’s immune system in fighting tumors. If Titmas chose to participate with Ellie, the goal would be to shrink the dog’s cancer until it was small enough to surgically remove, as well as to gather data that might lead to the immunotherapy someday becoming a viable treatment for similar cancers in humans. Titmas and Ellie were in.
Every year, nearly 500 pets like Ellie participate in voluntary clinical trials at Cummings Veterinary Medical Center. At any one time, thirty to forty different studies are enrolling patients. While some trials gather information and test therapies for conditions specific to companion animals, many focus on diseases that occur in both pets and people—it’s that latter category that holds so much promise for improving the health of humans and animals at once.
“Dogs share many physiological similarities to humans, are exposed to the same environment, and get many of the same diseases,” London said. “Studying these naturally occurring diseases in dogs and other companion animals—a growing field known as comparative medicine—helps provide researchers and medical professionals with important information to potentially advance development of therapies for treatment in both species.”
Cheryl London first became interested in cancer while she was a student at Cummings School. After her graduation in 1990, she worked in a general practice in Maine, where her interest in oncology only deepened. “It was the dawn of the first wave of immunotherapy, so it was an exciting time in oncology,” London said, “and I saw a lot of cancer in the dogs and cats presenting to my clinic.”
She went on to complete a residency in veterinary medical oncology at the University of Wisconsin-Madison School of Veterinary Medicine, and earn a Ph.D. in immunology at Harvard University. Before joining the faculty at Cummings School in 2016, London was an assistant professor at the UC Davis School of Veterinary Medicine, and then the Teckla and Don Shackelford Professor at the Ohio State University, where she directed its veterinary clinical-trials office at the veterinary school and Translational Therapeutics Program at the OSU Medical Center. Along the way, she conducted groundbreaking research in comparative oncology that supported the development of toceranib (Palladia), the first cancer drug specifically approved for dogs, and several important anticancer therapeutics in people, including sunitinib (Sutent) and selinexor.
During her research, London developed firsthand experience in the potential benefits of comparative oncology. Traditional cancer-drug trials move from promising results in laboratory mice to testing the drugs with humans—only to fail more than 80 percent of the time in the translation. In part, that’s because the rodent models of cancer that are typically used to study new cancer treatments often do not accurately mimic human cancers. For example, the lifespan of a laboratory mouse averages less than two years, so cancer development is often accelerated to occur in weeks, rather than years as it does in humans. And rodents don’t exhibit many of the same side effects from treatment as people and dogs experience (mice don’t vomit, for one).
Many dog and cat cancers are difficult to distinguish from their human counterparts, including lymphoma, osteosarcoma (a bone cancer seen in large-breed dogs and adolescent children), and cancers of the skin, bladder, and breast. London says that by studying these diseases in pets with their complex immune systems and real-world health conditions—such as obesity and aging—researchers gain a better understanding of novel treatments and potential side effects that would be difficult to assess in laboratory animals. Quality of life is a critical component of therapies for pets and people, London noted, and that kind of information can’t be gathered from mice.
Today, Tufts is one of twenty-two academic centers in the National Cancer Institute’s Comparative Oncology Trials Consortium, a group dedicated to finding new ways to help humans and animals. London, who also has joint appointments at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences, works closely with faculty from the medical school and Tufts Medical Center, spending two days a week running an active laboratory research program on the Boston campus. Despite spending much of her time overseeing clinical studies in Grafton, her busy schedule working to grow the comparative-medicine focus at Tufts means she rarely gets to work directly with pet owners and patients. “There are days I really miss being a doctor on the clinic floor,” she said.
To get everything done, she often wakes during the early morning hours to jumpstart her day. Once in the office, each half-hour might find London submitting another grant application, crunching study data, or otherwise collaborating with one of her many research partners at the Broad Institute, the Dana-Farber Cancer Institute, Boston Children’s Hospital, or MIT, as well as a host of other academic institutions and industry partners.
“Cheryl is a rock star in the canine clinical-trials world, and she’s kind of a dynamo,” said Kristy Richards, an associate professor of biomedical sciences at the College of Veterinary Medicine at Cornell University, who is a research collaborator of London’s. And although it makes for busy days, London believes the end result of such deep collaboration always leads to better outcomes. “As I’ve gotten older, I’ve realized I have no desire to be a solo scientist,” she said. “You get better ideas when you are constantly challenged to think outside of the box, and that happens most often in the setting of collaborative teams, whose members contribute different sets of expertise.”
As comparative medicine becomes more widely accepted, London has been in increasing demand from industry partners, who tend to track her down. “Collaborators in industry usually seek out our program to help optimize a treatment before it enters human trials,” she said. And for that matter, patients and other researchers often find her, too.
Take Kristy Richards, who is also an oncologist and hematologist at Weill Cornell Medicine. She followed London’s work with interest for about a decade, but it wasn’t until 2017 that she finally got to partner with her. Together, they secured a five-year, $2.5 million grant from the National Cancer Institute of the National Institutes of Health through the Cancer Moonshot initiative. In a clinical study that soon will begin enrolling at Cumming School’s Henry and Lois Foster Hospital for Small Animals, as well as two Cornell veterinary clinics, Richards and London will evaluate new combinations of immunotherapies for treating canine B cell lymphoma, one of the most common tumors in dogs.
Because canine and human B cell lymphoma are closely related, the researchers hope to develop a chemotherapy-free treatment regimen that results in long-term survival in dogs, and then use their findings to design future human clinical trials. “These are trials that you often can’t do in mice,” Richards said, since lab animals lack the real-world immune systems that are being manipulated into attacking cancer.
The potential of immunotherapies has been much in the news recently. Research was recognized by two of the Nobel Prizes awarded this year, for instance. And former U.S. President Jimmy Carter’s melanoma, which had spread to his liver and brain, is in remission thanks to an immunotherapy. Similar results have been seen in patients with metastatic lung cancer. “These are illnesses doctors never, ever could treat effectively,” said Richards, “and we are amazed at seeing such dramatic and durable responses.”
However, Richards noted, immunology is still in its infancy, and therapies only work in human patients a fraction of the time, depending on the tumor type. “How do we know who it’s going to work in and can we figure out why?” she said. “Studying this in dogs with cancer can help us get the answers to these questions much faster and in an easier way.” The only way to push the field of immunology forward is to conduct more—and better—studies. And that’s another place where London’s deep experience is proving essential.
One of London’s many research specialties is an approach called gap analysis, a method to determine, as she puts it, what biomedical researchers “need to learn or optimize about their approach in animals before going into people.” On a recent Friday afternoon, Tufts veterinary oncologist Lisa Barber had asked London to participate in a brainstorming session that would turn out to show London’s talent for that kind of analysis in action.
Barber and London had met in the Clinical Trials Office for a conference call to discuss a potential therapy for squamous cell carcinoma, an oral cancer found in people and cats. A pharmaceutical company wanted more data on its drug, which showed promising results in mice. On the other end of the conference line were researchers from the company, who needed more data about the drug’s efficacy before the therapy could be tried in human patients.
London listened carefully as the investigators described their work, proposing a complex plan that would require multiple studies in many cats, involving varying drugs dosages, multiple biopsies, and more. After they finished, London jumped in with a few minutes of rapid-fire questions, distilling their objectives in real time. By the time the call ended, the investigators had an elegant plan for two, much-simpler studies laser-targeted on their objectives.
After the call, London and Barber took leave of each other—London to focus on the next item in her long to-do list, Barber to return to the Foster Hospital floor to help patients. With a promising new research plan in place, Barber couldn’t help but smile. “Watching Cheryl work,” she said later, “can be an amazing thing to see.”