Cancer is cancer, whether you have two legs or four. With that principle in mind, Flint Animal Cancer Center scientists, Drs. Steve Dow and Dan Regan, are collaborating with pediatric oncologists at Children’s Hospital Colorado to study a promising new therapy to treat metastatic bone cancer in both dogs and kids.
The Science behind the Study
Tumor progression depends on help from the immune system, specifically from a type of white blood cell known as an inflammatory monocyte. These monocytes, which eventually differentiate into specialized cells called macrophages, help promote survival of metastatic tumors, in part, by stimulating new blood vessel growth. Consequently, treatments that can block monocyte and macrophage activity can help prevent the spread of cancer to other parts of the body and treat existing tumors by removing immune suppression and blocking new blood vessel growth.
However, the Food and Drug Administration has yet to approve a drug that can be used to block monocyte migration for humans or animals. To overcome this barrier, Regan and Dow set out to find FDA-approved drugs that blocked monocyte migration as an unintended drug effect. The goal would be to repurpose these drugs as cancer immunotherapies. After a long search, they discovered a class of drugs known as angiotensin receptor blockers that demonstrated strong monocyte migration-inhibiting activity in multiple species (mouse, dog, human).
Regan and Dow selected one of the drugs in this class (losartan) to evaluate the effect in mouse tumor studies. These studies showed strong activity using losartan alone in helping control the growth of metastatic tumors. When combined with a second drug, sunitinib, a targeted cancer drug that also has immune-modulatory properties, studies in mice showed even greater activity.
From Lab to Patient
Based on laboratory results, the investigators designed a clinical trial to study the effects of losartan in dogs with metastatic bone cancer that had progressed to their lungs. At this stage of disease, few treatments have succeeded in extending life beyond approximately two months after diagnosis. For the study, scientists administered high-dose losartan with Palladia (toceranib), a targeted drug that has minimal activity against osteosarcoma, but does have immune-modulatory effects in dogs. Results from 16 dogs treated in this trial have been very encouraging, with 50 percent of the dogs responding and almost 30 percent experiencing actual tumor regression. Importantly, adverse events have been few and typical of those expected for Palladia treatment.
One Cancer. One Cure.
The striking similarities between osteosarcoma in dogs and humans make dogs the best animal system to study human bone cancer. Each year, more than 8,000 dogs are diagnosed with osteosarcoma. While bone cancer is more common in dogs, according to the Children’s Hospital Colorado, osteosarcoma usually occurs in school-age children and adolescents and is the sixth most-common type of cancer in this age group. The five-year survival rate for human patients with bone cancer that has spread only to their lungs is 40 percent (www.cancer.org).
The encouraging results of the losartan study in dogs and the discouraging survival rates in children with advanced osteosarcoma, prompted Regan and Dow to reach out to oncologists at Children’s Hospital Colorado. Both entities are members of the University of Colorado’s Cancer Center consortium and readily share information. Dow and Regan proposed a study using losartan in pediatric bone cancer patients with tumor metastases who have failed to respond to conventional treatment. Working with pediatric oncologists, Drs. Lia Gore, Carrye Cost, Margaret Macy, and Kelly Faulk, the combined team is now designing a clinical trial similar to the canine trial using high-dose losartan and sunitinib for pediatric bone cancer patients. The team hopes to begin enrollment this fall.
“These studies build on the important connections between the human and veterinary sarcoma fields first established by Drs. Ross Wilkins and Steve Withrow, and provide real-world evidence of the impact of the One Cure concept,” said Dow.
One Cure’s goal is to raise awareness and funding for the Flint Animal Cancer Center’s clinical trials program and other comparative oncology research to find better treatment options for both pets and people with cancer. Currently, both Children’s Hospital and Flint Animal Cancer Center are seeking funds to support the upcoming pediatric trial. The Shipley Foundation in Boston, a longtime supporter of CSU’s cancer center, funded much of the initial laboratory study and canine clinical trial. For more information about the trial, please email [email protected]. To learn how you can support this important work, please contact Torii Kapavik.
All gifts to One Cure support clinical trials and comparative oncology research at CSU’s Flint Animal Cancer Center. Please consider donating today.