Veterinarians team with cancer center researchers to benefit canine and human patients
UC Davis’ Comparative Oncology Program a national leader
Bailey is an ordinary Labrador mix pet from Chico. But what the dog has done may save a human life, perhaps many.
Bailey has come to the UC Davis Companion Animal Health Center at the School of Veterinary Medicine because she has non-Hodgkin lymphoma, and UC Davis has one of the very best veterinary schools in the country.
Bailey was enrolled in a trial that is part of the Comparative Oncology Program of the UC Davis Comprehensive Cancer Center. In comparative oncology programs, veterinarians collaborate with physicians who treat humans and conduct research using pet dogs. The idea is that what is learned from pets will be applied to human cancer. The UC Davis program is one of just a handful in the nation.
The opportunities provided through these programs contrast dramatically with what companion animals with cancer had just a few decades ago. In those days, veterinarians diagnosed cancer in a dog, and then put the animal down.
“The oncology group at UC Davis has been actively engaged in important clinical and basic science research for many years, and they have a long-standing interest in comparative medicine approaches,” says Melissa Paoloni, a veterinarian with the Comparative Oncology Program at the National Cancer Institute in Rockville, Md.
She says these efforts come at a critical time because there is a “growing difficulty in successful new oncology drug development.” Only five percent of new agents investigated for cancer treatment end up receiving approval from the Food and Drug Administration.
Bailey’s trial involved use of a drug called paclitaxel, (brand name Taxol). Many are familiar with this drug because it is used to treat breast cancer. Taxol is considered a highly potent chemotherapeutic agent, but also can cause a serious allergic reaction, which generally occurs because of a substance paclitaxel must be paired with to make it mix in water, Cremophor, allowing it to circulate in the blood stream.
Dogs cannot tolerate Cremophor.
But the paclitaxel used in Bailey’s trial does not contain Cremophor. Instead, the drug is encased in a shell developed in the laboratory of professor Kit Lam at the cancer center. The shell allows it to mix in water, which is necessary for systemic administration; the shell is not passive, as it contains molecules that actively target the tumor.
“The oncology group at UC Davis has been actively engaged in important clinical and basic science research for many years, and they have a long-standing interest in comparative medicine approaches.”
— Melissa Paoloni
In the early phase trial, which involved 12 dogs – including Bailey – veterinarians found a dose that was very well tolerated, says Michael Kent, an assistant professor and the veterinary oncologist overseeing the trial.
Bailey is probably not cured, but she did respond. When diagnosed, she had very enlarged lymph nodes in her neck; they shrunk following the treatments.
“She handled the drug really well, and she is through a few doses,” says Kent.
Bailey has a B-cell, non-Hodgkin lymphoma, a disease that normally kills dogs within two months if not treated. Dogs treated with standard chemotherapy can live about one year. Lymphoma is fairly common in dogs, as it is in people, making canines valuable for this kind of research.
Because dogs live with people, are exposed to the same environmental insults and get some of the same types of cancer, they make good study subjects.
“We’ve cured cancers in mice for years,” Kent says. “It hasn’t helped much. Often the cancers are so different from those in humans that it just doesn’t translate.”
Kent said his group started with lymphoma because lymphoma is relatively common in dogs and because the laboratory that developed the encapsulation process also has a molecule called LLP2A.
The molecule can be attached to the encapsulation, which is called a micelle. LLP2A is what researchers call a target molecule. It attaches to a receptor molecule on leukemia and lymphoma cancer cells. In this way, more of the drug goes directly to cancer cells, and less is lost in the body’s general circulation, where it can cause side effects.
Targeting might greatly improve the efficacy of drugs such as paclitaxel. Kent and others in the veterinary cancer clinic expect to test LLP2A in dogs with lymphoma soon.
While Kent’s project is the closest to clinical application, other projects are equally exciting, says Robert Cardiff, a professor of medical pathology and the program leader. One of those is an investigation into how cancer arises.
Until now, it has been thought that cancer occurs because as cells grow and divide their DNA mutates. Eventually, the theory suggests, a cell would get too many mutations and become cancerous.
But work being done by Alexander Borowsky, a pathologist working with Cardiff, suggests instead that there are cancer stem cells – existing cells with the potential to become cancer. They do not need gene mutations. They simply need the cancer genes they have to be turned on.
Borowsky has shown that one can take cells from an abnormal growth in a mouse that is not a cancer, and transplant it to the surface of a fat pad, which keeps it alive, and some of the transplanted cells will become malignant cancer.
The work is basic science on the origins of cancer, but it could ultimately have practical value. It means that one could perhaps identify the cells with the potential to become cancer and remove them. It also suggests that one could turn a cancer cell back to its pre-malignant state.