SickKids team receives $2.99 million USD from SU2C Catalyst program to develop combination therapy for most aggressive cancer predisposition syndrome

Collaboration is critical to the development of new therapies for childhood cancers. A team from The Hospital for Sick Children (SickKids), led by Dr. Uri Tabori, was recently awarded $2.99 million USD from Stand Up To Cancer, SU2C Catalyst® program to develop and investigate the optimal combination therapies for kids with the most aggressive childhood cancer predisposition syndrome called biallelic mismatch repair deficiency (bMMRD). This project, made possible by a grant from Bristol-Myers Squibb Co., is a collaboration between SickKids, and SU2C-St. Baldrick’s Foundation Pediatric Cancer Dream Team scientists.

Virtually all children with this predisposition syndrome will develop multiple different types of cancer in the first two decades of life. In a 2015 Nature Genetics study, the SickKids team described this unique group of cancers with the highest mutational load in any human cancer. “While most cancers grow progressively, accumulating genetic mutations over many years, we were shocked to find that children with bMMRD develop more mutations than any human cancers by far – as many as 20,000 cancer mutations in as little as six months,” says Dr. Uri Tabori, team leader for this project, and Staff Oncologist and Senior Scientist at SickKids.

Based on ongoing research to improve cancer treatment for these patients, the team believes that these cancers will be uniquely sensitive to treatment with immune checkpoint inhibitors, such as a drug called nivolumab. These drugs work by releasing the brake on the body’s immune system and allowing the immune system to fight against cancer. The first patients treated with these inhibitors were Canadian children and responded well. Since then, SickKids oncologist Drs. Eric Bouffet, Tabori and Morganstern has led the first international nivolumab monotherapy trial in ultra-hypermutant paediatric cancers.

This SU2C Catalyst grant enables the team to further investigate the prevalence of hypermutant human cancers, identify biomarkers that may predict the response to immunotherapy, and design clinical evaluation of combination therapies with nivolumab to increase therapeutic efficacy, thanks to collaboration with Bristol-Myers Squibb.

“Ultimately, our goal is to develop new methods for treating childhood cancers for which there is no curative treatment available and to use genetic sequencing methods to select the right treatment for the right patient,” says Tabori.  

This work is an example of how SickKids is contributing to making Ontario Healthier, Wealthier and Smarter www.healthierwealthiersmarter.ca.