effective treatment for advanced breast cancer. In Canada, one in nine women will develop breast cancer during their lifetime, and one in 29 will die of the disease. Before corning to Guelph in 2009,Viloria-Petit worked on breast cancer metastasis as a post-doc at Mount Sinai's Samuel Lunenfeld Research Institute in Toronto. There, researchers had learned how a molecule called transforming growth factor beta (TGFb) changes the cell's shape to promote tumour cell migration and metastasis. Last year she was part of a team that discovered that nucrovesicles made and secreted by normal cells near a tumour affect cancer's ability to spread to other body tissues. She says doctors might be able to target proteins in th ese microvesicles to halt cancer spread. That study was published in the journal Cell in late 2012. " It's an impo rtant example of how the environment of the tum o ur co ntributes to metastasis ." She's also looking at howTGFb helps cause angioge nesis. That process allows a tumour to spro ut new blood vesse ls to gain nutrien ts and oxygen. Hitting the common signalli ng networks activated by this protein in endothelial and tumour cells might provide a one-two punch, she says. "We want to target and simultaneously block what happens in tumour cells to prom ote metastasis and w hat happens in endothelial cells to promote angiogenesis." Many researchers work on one process or the other, but Viloria-Petit aims to understand both. She hopes to figure out how to disrupt the entire signalling network controlled by TG Fb. Besides breast cancer, this molecule is involved in tumour types such as colon and prostate cancer. She works with cell cultures using OVC's stored dog cell lines and collaborates with Toronto colleagues using robotic screening to identify different signalling molecules connected to and modulated byTGFb. Signalling in bone cancer is another focus of her lab.A particular problem in larger dog breeds such as greyhounds, osteosarcoma is highly metastatic and resistant to therapy. For dogs treated with both surgery and chemotherapy, only 30 per cent will survive for two years. In people, current therapies prolong life in only 30 per cent of patients. Osteosarcoma cells can produce large amounts ofTGFb proteins, and bone cells are
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THE PORTICO
the biggest source of this protein in the body. Viloria-Petit is using an osteosarcorna bank containing specimens of tumours from dogs treated at OVC, as well as cell lines derived &om those tun10urs. Along with pa tho biology professor GeoffWood and clinical studies professor Tony Mutsaers, she studies proteins expressed in those cell Ii nes and their connection to metastasis and therapy resistance. Connecting protein expression with patient survival and metastasis nught help scientists develop drugs to target those proteins, she says. Having access to OVC's anin1al cancer centre helps in drawing those connections. " I hadn't been exposed to veterinary patients before I came to Guelph," says Viloria-Petit, who studied biology and inummology in Venezuela and did her PhD at the University ofToronto. Her grandfa ther died of metastatic lung cancer w hen she was 14. "That was my first contact with metastatic disease; it intrigued me a lot. I couldn't understand how so mething that started in his lung ended up in his brain."
Models of disease Following veterinary studies at OVC, Geoff Wood studied cancer biology for his PhD and for a D.VSc. split between Guelph and his supervisor's labs at two Toronto hospital . He also worked at the Toronto Centre for Phenogenomics, where researchers use genetically engineered nuce to study a range of diseases . He returned to Guelph in 2007 to study bone cancer. Wood says dogs provide a more real-life look at ca ncer, particularly hum an forms of the disease. "Certain sponta neous tumours in dogs are very good models of disease . Until recently, we lacked a good model for human bone cancer." Working with tumour samples from the animal cancer centre, he uses whole-genome chips containing thousands of dog gene samples to search for cha nges linked to bone cancer. So far, he has pinpointed several possible culprit genes in comparative studies of mouse, dog and human genomes. Wood is also looking at tissue samples to study metastasis, specifica ll y by studyi ng gene ti c changes between primary tumour cells in bone and "met" cells in the lung. He's found at least one gene associated with post-chemotherapy survival . That's important for clinicians and pet owners deciding
on treatment options, he says . Wood's interest in cancer stems from pathology classes taken during hi s DVM studies. He was intrigued by the complicated mix of enviroru11ental, dietary and genetic factors involved in the disease. Retunung to Guelph made sense for two key reasons , he says. One draw was the planned animal cancer centre, a tangible sign of a growing ca ncer biology community embodied in ICC !. "There's a good connection between the clinic side and research - the barriers here are a lot less than in a human hospital."The other compelling factor was Guelph 's new Pathobiology/ Aiumal Health Building, which opened in late 2010.
Vaccine therapy A similar path took pathobiology professor Byram Bridle from stud ies at Gue lph into research elsewhere and then back to U ofG. A cancer inummologist, he returned in 2012, bringing hopes of developing a ca ncer vaccine that would use the body's inm1une system and viruses to fight the disease. His idea rests partly on so-called oncolytic viruses, which prefer to invade cancerous cells rather than normal ones. It ni.ade sense to use th ese viruses to get rid of cancer, he thought. But how to surm ount the body's inunune system, normally primed to find and destroy such invade rs' His answer: make th e viruses and immun e system work together. First, vaccinate a patient with proteins taken from the tumour to prime the immune system . Then inject an oncolytic viru s modified with the gene for that protein. That would trigger the immune system to attack the protein , including the original tumour, while the virus is left intact to invade the cancer cells. Having obtained proni.ising results in ni.ice, Bridle now plans to work with dogs and cats as the next step toward testing this seek- and-destroy approach in people. For both the immune system and viruses, a hallmark is their specificity, he says. "We can both kill tumour cells wi th high specificity and leave th e normal cells alone."With this approach, doctors would not have to pinpoint the precise location of the tumour target and could treat patients witho ut the toxic side effects of other forms of therapy, he says. This work effectively turns Bridle's graduate studies on end. For his PhD wit h