Man’s Best Friend in More Ways Than One
Cancer drug development typically begins with in vitro research before proceeding through varying degrees of investigation in cell lines and laboratory animals, eventually culminating in human clinical trials. However, this often arduous development path may now find an ally in a relatively new branch of oncology research, referred to as comparative oncology. Initiated and directed by Chand Khanna, D.V.M., Ph.D., the CCR Comparative Oncology Program complements translational research through the characterization of relevant and naturally occurring cancer models that develop in pet animals as a window to evaluate novel therapies.
Prince (Photo: Frances and Peter Way)
It was nearly Christmas when Prince, an amiable, nine-year-old Labrador retriever was diagnosed with oral malignant melanoma. His owners, Frances and Peter Way, wanted the best treatment for their companion, so when veterinarians at Colorado State University’s (CSU) Animal Cancer Center suggested a clinical trial, the Ways readily agreed. Prince’s melanoma was very aggressive, similar in many ways to human melanoma, and the Animal Cancer Center was part of a consortium, sponsored by CCR’s Comparative Oncology Program (COP), through which dogs are treated with experimental therapies to prepare for their use in human clinical trials. Prince was treated with a new immunotherapy and achieved a robust response, living for almost a year. “That’s a lot longer than we think he would have otherwise,” said Peter Way, from Fort Collins, Colo. “We were hoping for a cure, but we also knew this would help the science, and I was glad that Prince could participate. It fit his spirit and his attitude; he was a great dog.”
Addressing a Lost Opportunity
“It became clear to me that there would be great value in including pet animals with cancer within our CCR studies.”
To date, the COP has treated more than 150 dogs over the course of nine clinical trials conducted by its leadership of the Comparative Oncology Trials Consortium (COTC), a collaborative network of 20 veterinary schools from around the country overseen by Melissa Paoloni, D.V.M. Khanna conceived of the COP while he was a postdoctoral fellow in CCR, in the lab of Lee J. Helman, M.D. At the time, he was working on tumor metastasis and osteosarcoma, a bone cancer that occurs in pediatric patients and is also common in dogs. “It became clear to me that there would be great value in including pet animals with cancer within our CCR studies,” Khanna said. “There are very few human cancers that don’t also occur naturally in pet animals. To me, not learning from their cancers to help inform human clinical trials seemed like a lost opportunity.”
In 2004, with backing from Helman and Carl Barrett, Ph.D., then Chief of CCR’s Pediatric Oncology Branch and CCR’s Director, respectively, Khanna established the COP. Its mission, Khanna explained, is to improve the assessment of novel treatments for humans by treating pet animals—primarily dogs with naturally occurring cancers—while also trying to give these animals better quality of life by offering them the benefit of cutting-edge research and experimental therapies. “The ultimate goal was for NCI to engage the drug development community, and to lead a consortium of veterinary schools in a program to supply clinical research results that might accelerate new human treatments, and simultaneously help pet animals with cancer,” Khanna said.
A Logical Partnership
The Comparative Oncology Trials Consortium (COTC) is an active network of 20 academic comparative oncology centers, centrally managed by CCR’s Comparative Oncology Program. (Image: VSB Associates)
According to Khanna, enrolling pet dogs in clinical trials has the potential to offer some key insights into human drug research. Dogs routinely develop osteosarcoma, lymphoma, bladder cancer, head and neck cancer, malignant melanoma, and mammary cancer. Moreover, human and canine cancers are very similar with respect to their genetics and biological features. On a practical level, the compressed life span of a dog and the more rapid course of cancer progression makes it easier for scientists to evaluate the benefit of novel cancer therapy in a short period of time. Repeat biopsies are often easier to perform in dogs than they are in people, making canine pre- and post-dosing tissue studies to investigate drug-target interactions feasible. Additionally, thanks to the public release of the canine genome sequence in 2005, scientists can now understand the molecular changes that are associated with a treatment response and a treatment failure. And finally, the COTC studies spontaneously occurring tumors in pet dogs, which are far more similar to human cancer than tumors induced artificially in mouse models of cancer. “It’s also important to note that the COTC provides cutting-edge cancer treatment to pets whose owners might not otherwise be able to help them,” said Paoloni. “It can cost thousands of dollars to pay for cancer therapy in a dog, and unfortunately that puts it out of reach for many families, so our efforts can help both human and veterinary cancer patients.”
According to Khanna, COTC projects emerge from collaborations with the drug industry and other research organizations involved in cancer drug development. The COP then chooses participating sites based on their availability, access to advanced technology (such as PET scans, for instance), and other factors. Once approved, researchers at chosen sites enroll dogs according to eligibility criteria that—mirroring the situation with human clinical trials—can be very strict. For instance, many studies exclude dogs with other co- morbidities, such as renal failure or cardiac disease.