A pan-Canadian team has developed a new way to quickly find personalized treatments for young cancer patients, by growing their tumours in chicken eggs and analyzing their proteins.
The team, led by researchers from BC Children’s Hospital Research Institute and the University of British Columbia, is the first in Canada to combine these two techniques to identify and test a drug for a young patient’s tumour in time for their treatment.
Their success in finding a new drug for the patient, described this week in EMBO Molecular Medicine, shows how the study of proteins, known as proteomics, can be a valuable complement to the established study of genes (genomics) in real-time cancer therapies.
Holding the chicken egg avatar on which a tumour is growing to be used for evaluating treatments.
The work was a collaborative effort of PROFYLE (PRecision Oncology For Young peopLE), a key initiative of the Canadian pediatric cancer network ACCESS (Advancing Childhood Cancer Experience, Science and Survivorship) that brings together more than 30 research and funding organizations and over 100 investigators from across Canada to improve cancer outcomes for children and young adults.
The study by co-lead authors Dr. Georgina Barnabas, a postdoctoral researcher in Dr. Philipp Lange’s lab, and Tariq Bhat, a PhD student in Dr. James Lim‘s lab, focused on an unnamed patient diagnosed with a rare pediatric cancer that resisted conventional treatments.
While genes carry the instructions to make proteins, proteins themselves are the functional building blocks of our cells. Most drugs work by changing the activity of proteins, so the team wondered if proteomics could uncover hidden weaknesses in tumours that genetic testing alone might miss.
After standard chemotherapy had failed and the tumour became resistant to a drug selected by genomics, no clear drug candidates emerged from further genetic testing. But instead of stopping there, the team turned to proteomics and discovered that the tumour’s metabolism relied heavily on an enzyme known as SHMT2.
But by looking at the tumour’s proteins, we found a critical metabolic weakness that we could target with an already approved drug.
– Dr. Philipp Lange
“With genomics alone, we couldn’t find a clear treatment option,” said Dr. Lange, who, along with Dr. Lim and clinician Dr. Rebecca Deyell, are senior investigators with the Michael Cuccione Childhood Cancer Research Program at BCCHR. “But by looking at the tumour’s proteins, we found a critical metabolic weakness that we could target with an already approved drug.”
The researchers’ strategy was to use sertraline, a common antidepressant, to inhibit SHMT2 and cut off the tumour’s access to a key energy source.
To test their idea, the team used a method that involves growing a small piece of the patient’s tumour on a chicken egg, serving as an avatar host for the tumour. Growing an identical tumour outside the patient gave them a way to test for personalized drug responses in a matter of weeks.
This technique speeds up the process of evaluating a treatment option in a way that simply wouldn’t be possible with traditional methods.
– Dr. James Lim
“This technique speeds up the process of evaluating a treatment option in a way that simply wouldn’t be possible with traditional methods,” said Dr. Lim. “We could quickly confirm whether the drug we identified through proteomics could actually work for the patient’s tumour.”
The chicken egg avatars are part of the BRAvE initiative (Better Responses through Avatars and Evidence) at BCCHR, which connects clinics with research labs at the hospital.
The team presented their results to a panel of experts established by PROFYLE, who considered sertraline as the best treatment option for the patient at the time. The results were promising but not a cure. After beginning sertraline treatment, the patient’s tumour growth slowed but did not stop, meaning additional treatment was still needed.
“While there is more work to be done, this study shows that our approach can deliver personalized treatment recommendations fast enough to actually help patients with rare and difficult-to-treat cancers,” said Dr. Lange. “We now hope to expand this method to other children to identify effective treatments faster across the country.”
Credit: UBC News release
