11:58am Friday 22 September 2017

Accelerating the search for new cancer therapies: SickKids scientists find new twist on drug screening to treat common childhood cancer

The study is published in the August 18 advance online edition of EMBO Molecular Medicine.

The idea of repurposing existing medications is not new, but testing them on the cells isolated directly from children and that are thought to be responsible for the spread and regrowth of their tumours is novel. According to the study’s principal investigator, Dr. David Kaplan, there is an urgent need to develop new treatments for neuroblastoma. Less than 40 per cent of patients over the age of one survive this cancer, and the disease usually relapses, aggressively spreading or metastasizing to other parts of the body.
 
“We conducted our drug discovery by targeting the cells that we think are responsible for the cancer coming back,” says Kaplan, Senior Scientist at SickKids and Professor in the Department of Molecular Genetics at the University of Toronto. “This is a new way of developing drugs for kids, as we are taking the patients’ own cancer stem cells and testing them in the lab.”
 
The team, led by Dr. Kristen Smith, postdoctoral fellow in Kaplan’s laboratory, had two main goals in this project: to eliminate the cancer cells and to do this without harming healthy cells. Since cancer therapies like chemotherapy kill good cells along with the bad, striking this delicate balance – even in adult cancers – can be challenging. This risk of toxicity is amplified in children, whose growing bodies are particularly vulnerable to the side-effects of powerful treatments, which can result in developmental problems and a higher risk of developing cancers as adults. As a result, some drugs that are proven to effectively treat cancer in adults cannot be used in children, leaving few options for some young patients.
 
Neuroblastoma, a solid tumour found outside the brain in the nervous system, is the most frequent cause of disease-related death in children.
 
The research team identified two drugs, DECA-14, a version of an antibiotic that is found in some mouthwashes, and rapamycin, a drug that is used to prevent organ rejection in children who have received transplants. Both medications were found to be effective in treating mice with neuroblastoma and were non-toxic to the normal stem cells from children.
 
The researchers were able to begin a clinical trial much faster than if a new drug was being developed since one of the therapies, rapamycin, had already been proven to be safe in children, with established protocols that outline the quantity and frequency of treatment. On the basis of this study, a SickKids-led North American Phase I clinical trial is already underway in collaboration with CHU Sainte-Justine in Montreal, as well as two centres in the US. The trial will evaluate rapamycin in combination with the chemotherapy drug vinblastine, for paediatric solid tumours. This trial is led by Dr. Sylvain Baruchel, Staff Oncologist and Senior Associate Scientist at SickKids and Professor in the Department of Paediatrics at the University of Toronto, who was also a collaborator on this study.
 
If the clinical trial shows positive results, this could be the beginning of a personalized medicine approach, Kaplan says. “Our dream is that children will come to SickKids, we’ll isolate their cancer stem cells, screen them with libraries of drugs and find out whether Patient A will respond to Therapy B.”
 
This research was funded by the Stem Cell Network in partnership with the James Fund for Neuroblastoma Research, and Solving Kids’ Cancer. This study was also supported by the Canadian Institutes of Health Research, Canadian Cancer Society Research Institute, Lilah’s Fund, Shania’s Sunflower of Hope, Sam’s Day, the Ontario Institute for Cancer Research, the Terry Fox Research Institute, and the McLaughlin Centre and SickKids Foundation.
 
When the new SickKids Research & Learning Tower opens its doors, Kaplan’s lab will be relocated to the Cancer, Stem Cells & Regenerative Medicine neighbourhood. The shared resources and close proximity to colleagues in other scientific disciplines will encourage novel ideas and may result in collaborations between researchers who may not otherwise interact.

About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system.  SickKids is proud of its vision of Healthier Children. A Better World.™ For more information, please visit www.sickkids.ca.

About SickKids Research & Learning Tower
SickKids Research & Learning Tower will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs.  The Tower will physically connect SickKids science, discovery and learning activities to its clinical operations.  Designed by award-winning architects Diamond + Schmitt Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Tower will create an architectural landmark as the eastern gateway to Toronto’s Discovery District.  SickKids Research & Learning Tower is funded by a grant from the Canada Foundation for Innovation and community support for the ongoing fundraising campaign. For more information, please visit www.buildsickkids.com.

For more information, please contact:

Matet Nebres
Manager, Media Relations
Communications and Public Affairs
The Hospital for Sick Children
Tel: 416-813-6380
Fax: 416-813-5328
e-mail: matet.nebres@sickkids.ca

Suzanne Gold
Communications Specialist – Media Relations
Communications and Public Affairs
The Hospital for Sick Children
Tel: 416-813-7654 ext. 2059
Fax: 416-813-5328
e-mail: suzanne.gold@sickkids.ca


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