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About Sickkids
About SickKids

August 3, 2009

SickKids scientists discover a potential treatment for a previously untreatable bone cancer

TORONTO – While recent advancements in cancer research have led to longer survival rates, there are still some cancers that are not responsive to existing treatments. Chondrosarcoma, a rare bone cancer that develops in the bone cartilage, is one of the cancers that is not effectively treated with chemotherapy. Scientists at The Hospital for Sick Children (SickKids), Mount Sinai Hospital and the University of Toronto have found a novel approach to treating this disease.

The research team identified what causes benign (non-cancerous) cartilage tumours to transform into malignant (cancerous) ones. Then they found a possible therapy to prevent and treat the cancer. Clinical trials are now underway to test the effectiveness of a combined drug therapy to treat these tumours. The research is published in the August 4 edition of Cancer Cell.

“This work really shows how understanding fundamental science can identify a potentially better treatment for what is otherwise an untreatable cancer,” says the study’s principal investigator Dr. Benjamin Alman, a Senior Scientist and Head of Orthopaedic Surgery at SickKids, and Professor of Surgery at the University of Toronto. “In the future we hope to help identify other pathways like this one that can be targeted with new treatments.”

The project began 10 years ago when the researchers looked at how cartilage tumours were formed. Typically, bones start off as cartilage. When they turn into bone, some cartilage stays behind and becomes the person’s growth plate – this is what makes the body grow over time. The scientists found that benign tumours called endochondromas were forming next to the growth plate. They discovered a mutation in the tumour cells that they believed would change the way the cartilage cells mature and would make them more prone to developing into a tumour.

To test their finding they used genetically modified mice called Gli2, that had a growth plate mutation. The mice developed endochondromas and some of these benign tumours went on to become malignant. The scientists then set out to find out what causes benign tumours to change into malignant ones.

“The idea is to use this information to identify therapeutic targets, or at least find ways to prevent benign tumours from becoming malignant,” says Alman.

When the researchers crossed the Gli2 with a mutated gene called P53 (a tumour suppressor gene), chondrosarcomas (malignant cartilage tumours) were formed in the mice.

The next step was to identify what the Gli2 mice and P53 mice had in common: a
gene called IGFBP3 that appeared to be regulated by the signaling in both Gli2 and P53 mice.

In benign tumours there is a higher level of IGFBP3; in malignant tumours it is lower. The researchers also found this to be the case in humans. This led them to the novel approach of targeting the IGFBP3 gene found in the Gli2 and P53 mice to treat chondrosarcomas.

Currently, there are two drugs that are being used in clinical trials that have been developed to treat both mutations individually. As a result of this study, new clinical trials are already underway to determine the effectiveness of both drugs in combination in treating chondrosarcomas.

“In the end we hope to develop a multi-drug regimen that will work,” says Alman. “We may have one drug that will prevent people from getting tumours and other drugs that will treat tumours after they have developed. The intent would be to make treatments that are more effective and less toxic for the patient.”

This research was supported by the Canadian Institutes for Health Research, Canada Research Chairs Program and SickKids Foundation.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

For more information, please contact:

Matet Nebres
The Hospital for Sick Children
Phone: 416-813-6380
email: matet.nebres@sickkids.ca

Suzanne Gold
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
email: suzanne.gold@sickkids.ca