New Canadian research points the way to preventing childhood cancer

February 8, 2012 - New research by Toronto scientist, Dr. Rod Bremner, Head of Genetics at Toronto Western Hospital may, one day, offer a way to prevent retinoblastoma. Retinoblastoma is a devastating childhood cancer of the eye that occurs in ~1 in 20,000 babies, usually in the first year of life. The condition is caused by genetic mutations that can affect one or both of the child’s retinoblastoma tumour suppressor genes (RB).
In children with only one mutated RB gene, each cell still has one healthy gene. None-the-less, a RB+/- child is still highly susceptible to retinoblastoma and to other cancers throughout life. One well-known person affected by retinoblastoma was famed Canadian guitarist, Jeff Healey, who was blind because of the disease, and died due to a secondary cancer in his early forties.
Through extensive genetic and biochemical studies of retinoblastoma-prone mice, Dr. Bremner and his colleagues found that retinoblastoma tumour growth requires high activity of two proteins, E2f and Cdk. The team treated pregnant tumour-prone mice with drugs to lower the activity of either of these proteins. After treating the mothers for only a single week during a critical period of the pregnancy, the likelihood of the newborn mice developing tumours was drastically reduced.
“Our results suggest that it might be possible to limit tumour growth in the eyes of RB+/- children,” says Dr. Bremner. “It is particularly encouraging that only a single week of treatment had such a dramatic protective effect.” The team will now continue studies in which newborn mice are treated directly, to see if limiting the activity of E2f and Cdk can have an ongoing preventative effect, potentially reducing both retinoblastoma and the development of other cancers. The drugs will also be tested in mice that already have tumours to determine whether they can slow or stop the growth of an existing tumour. 
Glen Wade knows about the ongoing risks of retinoblastoma, he was blinded by the disease as a child. He developed retinoblastoma in his left eye at age two and then his right eye at age four. Now a special projects manager at Rogers in Kitchener, he has also recovered from a secondary cancer, sarcoma, diagnosed six years ago and now in remission.
“I am excited and hopeful about Dr. Bremner’s discovery,” Glen says. “Retinoblastoma is hereditary, so the possibility I will pass this on to my future children is always on the back of my mind. It would be a comfort to know treatments could prevent future generations from being affected.” 
This research was funded by the Foundation Fighting Blindness, which has supported Dr. Bremner’s research since 2005. The Foundation Fighting Blindness supports research to advance the treatment of genetic forms of blindness primarily retinal degenerative diseases, which cause vision loss and blindness due to the slow deterioration of the retina. Treatments that limit the activity of E2f and Cdk may also be useful in the treatment of the degenerative eye disease retinitis pigmentosa.
“This is a prime example of how research can be synergistic,” says Dr. Valerie Wallace, Chair of the FFB’s Scientific Advisory Committee, Director of Vision Research at the Ottawa Hospital Research Institute and Associate Professor in the Faculty of Medicine at the University of Ottawa. “Dr. Bremner studies the intricate biochemistry of the retina and then explores the impacts of his findings on both cancer and degenerative eye disease. By supporting excellent science, the Foundation Fighting Blindness works to make a difference in the lives of many people with visual impairments.”
Dr. Bremner’s research was also supported by grants from the Ontario Institute for Cancer Research and the Canadian Institutes of Health Research. This research was published online January 30, 2012 in the journal, Oncogene.
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