health

Using genes to individualize cancer treatment

Of all the eight billion people on the planet, no two individuals share the exact same genetic makeup.

These genetic variations are responsible for different responses and treatment outcomes in different people.

Areas of study such as precision medicine and pharmacogenomics – the study of how a person’s genes influence their response to medication – involve developing treatment strategies tailored to each individual. This helps researchers find better ways to improve overall health outcomes and revolutionizes medicine from a “one size fits all” perspective to more patient-specific treatment.

University of Manitoba assistant professor of biochemistry and medical genetics, Britt Drögemöller, explained that “when we look at modern medicine, I think it’s really brought a big improvement in the way we can treat disease.”

The problem for her right now is that “treatments don’t work the same for all individuals.”

Drögemöller uses precision medicine and pharmacogenomic techniques to understand how genetic differences between individuals influence treatment response.

“We really want to make sure that the treatments we use are maximally capable of treating a disease, but also with minimal safety risks,” Drögemöller said.

“That’s why I think using this pharmacogenomics approach to precision medicine is so, so important, that we can start to think of individuals as individuals and treat them accordingly.”

Drogemoller gained initial interest in the field of human genetics through her undergraduate level genetics classes.

“I really liked the way we can find specific genetic variants that can explain so much,” she said.

Her research now mainly focuses on the side effect of the anti-cancer medication cisplatin, in particular the toxic effects on the ear.

Cisplatin works to reduce or stop rapidly dividing cells. It is widely used in chemotherapy, but its ability to cause damage to the ear is a major limitation. Up to 80 percent of people treated with cisplatin experience hearing loss.

“This can be really devastating, especially for young children who are still developing their language skills,” says DrögemOsaid ler. “If they also lose the ability to hear, developing language skills can become very difficult and can have an impact on their lives.”

Previous research has attempted to determine why some experience hearing loss as a result of treatment, while others have failed to attribute this selective hearing loss to factors such as age and the amount of cisplatin doses received.

However, Drögemöller found that an individual’s genetics account for about 40 percent of this variability.

“We really want to compare people who get hearing loss to people who don’t get hearing loss and see what differences we can see in their genetics,” she said.

In complex human genetics, an interplay of multiple genetic variants determines the differences between populations. These different genetic variants all work together to increase or decrease disease risk.

A predictive value called a “polygenic risk score” measures disease risk by adding up the different genetic risk variants an individual has into a single score.

By using these predictive polygenic scores, Drögemöller can quantify the likelihood that a person will experience cisplatin-induced hearing loss.

“That’s helpful if you want to know before giving treatment, improve hearing loss monitoring, and consider alternative treatments,” she explains.

“Obviously we don’t want to compromise the ability to treat cancer, so it’s always important to keep that in mind when considering treatments in patients as well.”

This information can also be used to develop improved treatments for patients by administering a hearing protector to prevent hearing loss during cisplatin treatment.

Polygenic scores are a promising tool for risk prediction, and their application to pharmacogenomics opens up new possibilities for improving treatment outcomes. They are currently being applied in coronary heart disease to determine which treatments are best for an individual.

“It’s a relatively new field, so I think we’re still working on applying it to more areas,” added Drögemöller.

In addition, Drögemöller examines age-related hearing loss using data from the Canadian Longitudinal Study on Aging – a long-running national study of a cohort of approximately 50,000 people’s changing health determinants as they age.

“We can use this information to identify genetic variants that cause age-related hearing loss or are associated with age-related hearing loss,” she said.

“Once we understand what increases people’s risk of age-related hearing loss, we can figure out ways to prevent it or determine who is going to experience it so they can take preventive measures.”

Overall, Drögemöller stimulates further public interest in pharmacogenomic and precision medicine research.

“There are so many opportunities in the field,” she said. “I think computational biology in particular offers so many job opportunities.”

“Even if you’re not interested in staying in academia, there are so many biotech companies, and lots of industry opportunities as well, where these kinds of skills can be really valuable.”

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