Dr. Richard Kim has high hopes. Not only does he want to see genetic testing become a routine part of prescribing certain medications, he hopes Western and London Health Sciences Centre (LHSC) will soon be a “health-care innovation hub,” where this practice is perfected and sought after in the training of future physicians.
A recent influx of $4.4 million in funding to his lab will go a long way towards these goals, said Kim, a clinical pharmacologist who is a professor in the Schulich School of Medicine & Dentistry and the Wolfe Medical Research Chair in Pharmacogenomics.
The funding expands an already existing personalized medicine program at LHSC, developed by Kim, and comes from the Ontario Research Fund (ORF) with matched contributions from Thermo Fisher Scientific and donor funding through London Health Sciences Foundation.
Pharmacogenomics – the study of genetic changes which alter the way a person responds to individual drugs – is an integral part of personalized medicine. Because of Kim, LHSC was the first hospital in Canada to have doctors adjust medication doses – or avoid certain medications – based on an individual patient’s genetic profile.
Genetic variance plays a role in how a patient metabolizes and responds to commonly prescribed drugs. For some individuals, certain medications can cause adverse effects, while some drugs can be toxic, deadly even after just one dose. Adverse drug reactions are the fourth leading cause of death among hospitalized patients and cost the Canadian health-care system more than $5 billion a year.
While Kim’s research team has looked at genetic profiling with a number of drugs to date, its current focus is on offering genetic testing for cancer patients prescribed 5-fluorouracil, a commonly prescribed chemotherapy drug that has a high toxicity but is essential in treating common cancers such as those that affect the bowel, stomach and neck.
“For commonly diagnosed cancers, chemotherapy is the main option. Currently, approximately 50 per cent of patients suffer significant chemo-related toxicity that often results in hospitalization or emergency room visits. And while it’s rare, these things happen; there are people who die from a single standard dose of chemotherapy,” Kim said.
Oftentimes, this is attributed to chemotherapy being generally toxic, he added, but genetics play a key role for some individuals.
“We now know certain kind of chemotherapeutic agents are dependent on genetically variable genes that are involved in their metabolism or deactivation. A large effort has been going into providing testing for a gene called DPYD – this is a key gene involved in the deactivation of 5-fluorouracil,” he continued.
“We’ve really made an effort to provide what we call pre-emptive genotyping; we see the patient before they undergo chemotherapy, without delaying the treatment timeline. Oncologists at our cancer centre have all seen the benefit of using genomics-guided testing, so they currently refer all of their patients who are prescribed 5-fluorouracil to my clinic.”
Oncologists at LHSC’s London Regional Cancer Program refer patients for testing before their first dose of 5-fluorouracil. Within a few days, Kim’s team meets with the patient and performs a genotyping test to predict their response to the drug. A full report is generated and sent back to the referring oncologist. If it’s predicted a patient will respond poorly to the drug, the team follows clinical guidelines to make recommendations to the patient and the referring physician. This often involves changing the dose or finding an alternative therapy.
Kim’s team will study the outcomes of any patients referred to the program, including hospital stays, emergency department visits and physician visits. These patients will be compared to others in the province using provincial health-care data from the Institute for Clinical Evaluative Sciences.
The team hopes to demonstrate they are able to provide patients with genomics-guided medication dosing and selection on a large-scale, in real-time, in the real-world scale.
“In some countries, hospitals have mobilized to offer these types of testing as part of chemotherapy, but in Canada, no one does that. On a personal level, as a physician, it’s really gratifying, to be able to reduce suffering by introducing things that would not have been done. For sure we have mitigated potentially life-threatening toxicities,” Kim added.
ORF support has likewise enabled a crucial interdisciplinary component for Kim’s research.
“We’ve been really fortunate to collaborate with co-investigators who are part of this grant – from Computer Science, Epidemiology, Biostatistics as well as Engineering. The Computer Science folks will help us with machine learning. The Engineering folks will help us with secure encryption technologies to ensure privacy of patient information. Ivey Business School is also involved in terms of how we can demonstrate the value of this approach and how we can create a business model that can be adopted based on our current model. It is what needs to be done to solve fairly significant health-care problems,” Kim explained.
“Our hope is that we start a kind of beginning of what we have articulated as a health-care innovation hub. We want to be the centre of excellence for training the next generation of physicians and scientists in genomic technology, where we can be a reference centre for helping others look after patients with genomics-guided medication dosing,” he continued.
“Ultimately, we want to demonstrate to the Ministry of Health and Long-Term Care that genomics-guided patient care strategies for drugs that are known to have genetic dependence and toxicity are feasible so that eventually, they will provide funding to the hospitals to be able to provide a test as part of hospital diagnostics.”
Through the London Health Sciences Foundation, Kim’s research has seen significant contributions, including $2.24 million from LHSC’s Auxiliary and $300,000 from 3M Canada.