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New approach accelerates personalized cancer treatment in young patients
Experts from Canada have developed a new way to quickly tailor personalized treatments for young cancer patients by growing their tumors in chicken eggs and analyzing proteins.
The team, led by researchers from the University of British Columbia and the BC Children’s Hospital Research Institute, is the first in Canada to combine the two methods to identify and test a drug to treat a tumor in a young patient in a timely manner.
Their success in finding a new drug for the patient, described today in the journal EMBO Molecular Medicine, shows how the study of proteins, known as proteomics, can be a valuable addition to the well-established study of genes (genomics) in real-time cancer therapy.
The work was conducted as a collaborative effort of PROFYLE (PRecision Oncology For Young PeopLE), a key initiative of Canada’s ACCESS (Advancing Childhood Cancer Experience, Science and Survivorship) network, which brings together more than 30 research and funding organizations and more than 100 researchers from across Canada to improve cancer outcomes in children and young adults.
The study, led by Dr. Georgina Barnabas, focused on an unnamed patient with a rare type of childhood cancer that had not responded to traditional treatments.
Proteomics: a supportive approach in treatment identification
While genes contain instructions for making proteins, proteins themselves are the functional building blocks of our cells. Most drugs work by altering the activity of proteins, so the team wondered if proteomics could uncover hidden weaknesses in tumors that genetic testing might miss.
After standard chemotherapy failed and the patient’s tumor became resistant to the drug identified through genomics, further genetic testing yielded no drug candidates. Not stopping there, the team turned to proteomics and discovered that the tumor’s metabolism is heavily dependent on an enzyme known as SHMT2.
“With genomics alone, we couldn’t find an obvious treatment option,” the researchers say. – But by studying the tumor 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 tumor’s access to a key energy source.
Reproduction of a tumor in a chicken egg
To test their idea, the team used a method that involves growing a small fragment of a patient’s tumor in a chicken egg, acting as an avatar host for the tumor. Growing an identical tumor outside the patient allowed them to test a personalized response to drugs in a matter of weeks.
“This technique speeds up the process of evaluating a treatment option in a way that traditional methods simply could not,” says the principal investigator. -“We can quickly test whether a drug we’ve identified through proteomics can actually work on a patient’s tumor.
The chicken egg avatars are part of the BRAvE (Better Responses through Avatars and Evidence) initiative at BCCHR, which connects clinics with the hospital’s research labs.
The team presented their findings to a panel of experts from the PROFYLE project, who found sertraline to be the best treatment option for the patient at that time.
Encouraging results, even though there is still a lot of work to be done
The results were promising but not curing. After starting treatment with sertraline, the patient’s tumor growth slowed but did not stop, which meant additional treatment was needed.
Although the scientists still have a lot of work to do, this study shows that their approach can provide personalized treatment recommendations quickly enough to actually help patients with rare and hard-to-treat cancers. Now we can look forward to applying this method in other children to find effective treatments more quickly.
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