Medical Innovation
Geneticists examine DNA structure on this glass board as they work to develop new precision therapies. supplied
Leading-edge research and treatments are driving the future of medicine
The discovery of a recurrent gene mutation in a British Columbia Cancer Research laboratory 20 years ago launched a new field in cancer biology. It also paved the way for the development of a personalized therapy to treat more than 20 different cancers, including the rare thyroid cancer of an Alberta child who now enjoys horseback riding, gymnastics and playing with Lego.
The discovery of the cancer-causing gene mutation – a fusion of the Neurotrophic Tyrosine Receptor Kinase to another gene named ETV6 (now known as an NTRK gene fusion) – by Dr. Poul Sorensen’s laboratory, the subsequent drug development and its eventual approval in 2019 took too long, says Dr. Sorensen, a Distinguished Scientist at the BC Cancer Agency and a professor in the Department of Pathology and Laboratory Medicine at the University of British Columbia.
The 1998 discovery and subsequent identification of NRTK fusions in many tumour types resulted in a new approach in treating and targeting tumours. Known as tumour-agnostic therapy, the approach more precisely targets a genetic alteration driving the growth of a tumour, not the specific tumour type.
The breakthrough discovery led to the development of the drug larotrectinib by Loxo Oncology and licensed by Bayer Pharmaceuticals. It marked the first time Health Canada approved a tumour-agnostic treatment.
One of the first patients to benefit from the drug is Ashton Leeds. Ashton was just five years old in 2015 when his mother Kayley found a lump in his neck, later diagnosed as Stage 4 thyroid cancer. Doctors in Calgary, Alberta, referred him to the Hospital for Sick Children in Toronto (SickKids) for surgery.
At SickKids, Ashton’s parents agreed to genomic testing, and the sequences were later included in the Kids Cancer Sequencing (KiCS) program, a genetic database for rare pediatric cancers.
After the initial surgery and treatment, Ashton was stable for two years.
“In 2017, we noticed a change in his breathing, and he had less energy – cancer was found in his lungs,” recalls Kayley Leeds. “We were devastated when we were told no other treatment could help him.”
However, about a month later, a phone call from the KiCS program let them know the cancer was caused by an NTRK gene fusion. Soon after that, there was news of a clinical trial.
“It seemed like the sun peeking through the clouds; we were not sure what would happen, but we wanted to try because we now had an option,” says Ms. Leeds.
Ashton was enrolled in the clinical trial at Seattle Children’s Hospital, and the positive results have enabled the now 10-year-old to return to a normal life.
“We feel incredibly lucky that a series of events allowed him to receive the treatment – if one thing had been different, we wouldn’t be where we are today,” says Ms. Leeds.
Ashton’s treatment is an example of precision medicine, seen by many to be the future of medicine as new research and treatments are enabling patients to benefit from more precise therapies.
While Dr. Sorensen, the first academic to win the annual Bloom Burton Award, is thrilled to know his research has resulted in a treatment for patients like Ashton, he believes that a more comfortable liaison between the public academic sector and private industry would result in more rapid advancements.
The perception that Big Pharma works only for shareholders is an oversimplification, says Dr. Sorensen.
“I believe that most of the people in the industry, if not all of them, really want to do good for society,” he adds.
This perspective was evident by the positive interaction between academia and the private sector at the Bloom Burton Award gala. “I sensed everyone was there for the betterment of society,” he recalls.
Explaining the role of precision medicine, Dr. Shurjeel Choudhri, senior VP and head of Medical and Scientific Affairs at Bayer Canada, says we are entering a new era. As we gain a better understanding of cancers and the alterations that drive them, therapies will become more precise, targeting specific gene alterations and mutations associated with a person’s cancer.
Dr. Choudhri anticipates changes in the way the health system views personalized and precision medicine. Although today there tends to be a focus on the price of a drug, the health-care system [in Canada] should consider new treatment advances in the context of the overall benefit and value that these products provide to both patients and to the overall health-care system.
“In order to provide real value to Canadians, our system has to get better at recognizing patient outcomes as a part of the value assessment,” he says.
In the case of precision medicine, there needs to be a recognition that such treatments could provide a material benefit to a select number of patients, as well as the overall health-care system. While the costs are higher when compared to traditional therapies, the patient value is far more significant. From improved outcomes to fewer side-effects, such therapies also tend to result in less frequent visits to hospitals, resulting in an overall benefit to the healthcare system.
Looking to the future of medicine, Dr. Choudhri says the converging trends of precision medicine and digital technology that enables activities like remote monitoring will drive the next generation of medicines.
On the other hand, Dr. Sorensen maintains that biology and preclinical studies must move along in parallel with discovering genetic alterations.
“We also need more international collaborations,” he adds. “I think team science is where medicine is going because different subspecialists bring in different expertise. And so, I think medicine in the future needs to go not only across countries, like Canada, but also across borders and especially across different disciplines, such as academia and industry.”
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