This is how a small tropical fish can guide therapies for children with cancer

The Berman Lab at the CHEO Research Institute led a study that looked at how Zebrafish models are an effective tool for children cancer therapies. (Peter Szperling/CTV News Ottawa)

What do Zebrafish and kids cancer have in common?

New research reveals that a small tropical fish can help guide personalized medicine and tailored therapies for some of the most challenging pediatric cancer cases, according to the CHEO Research Institute.

A first-of-its-kind proof-of-principle study was led by the Berman Lab at the CHEO Research Institute/University of Ottawa and facilitated in collaboration with two national precision oncology projects, Canada’s Precision Oncology For Young People and Australia’s Zero Childhood Cancer (ZERO).

The CHEO Research Institute says the study shows that preclinical zebrafish models are an effective tool to help guide clinical decision-making in real time for challenging pediatric cancer cases.

“Using this more personalized approach, we’re trying to find drugs that more specifically target that specific cancer, so that we have higher cure rates and fewer side effects,” Dr. Jason Berman tells CTV News Ottawa.

“It brings hope to patients and their families that we’re doing things differently right here in Ottawa.”

Berman says the current traditional approach to curing childhood cancers is, “a little bit of a one size fits all.”

He offers the analogy of “using a cannonball to kill a fly on the wall. We use chemotherapy, which is a fancy word for drugs that target cancer cells, but they really don’t just target the cancer cells.”

Berman says, with using this more personalized approach, “We’re trying to find drugs that more specifically target that specific cancer, so that we have higher cure rates and fewer side effects.”

How does it work?

According to the CHEO Research Institute, the larval zebrafish model holds a “significant promise to improve the efficiency of evaluating personalized treatment options for the greatest number of pediatric patients with cancer, providing much-needed hope and enhancing the quality of life for kids undergoing cancer treatment.”

The study, published in Cancer Research Communications, is the first to “directly compare drug responses in larval zebrafish patient-derived xenograft (PDX) models and mouse PDX models with actual clinical outcomes in pediatric cancer patients.”

“To provide personalized cancer treatments, clinicians create PDX models from a patient’s own tumour sample paired with genetic information to identify molecular targets for therapy and test possible disease-altering drugs,” the CHEO Research Institute said in a media release.

“Mouse PDX models are currently the most widely used for this purpose but can be limited in their application and effectiveness, particularly in providing real time clinically actionable guidance for certain high-risk cancer cases. Larval zebrafish PDX models offer several advantages that make them particularly valuable for pediatric cancer research.”

The CHEO Research Institute says “they can generate drug response data more quickly and cost-effectively, while requiring only a small tumour sample, compared to mouse models.”

“So, this is the first time that we’ve done a head-to-head comparison where we’ve looked at the zebrafish PDX model. So that’s patient derived xenograft taking cells from a childhood cancer patient from their tumour and putting them in the zebrafish and comparing that to the gold standard, which is mice,” Berman said.

He says one of the advantages is time.

“We need to be able to make decisions within days, at the most weeks, in order to decide what the best treatment is for our patient,” Berman said.

“And with the zebrafish, we’re able to put these cells in, watch how they behave because they’re fluorescently labeled, and the zebrafish are transparent. Add treatments just to the water and able to see those responses in seven to 10 days.”

According to the CHEO Research Institute, the study retrospectively examined tumour samples from 10 pediatric patients with high-risk cancers who had been enrolled on Australia’s Zero Childhood Cancer program.

“For each of these patients, their clinical response data to individual drug or drug combinations was available, as well as in most cases, drug response data from the mouse PDX established from their tumours,” the CHEO Research Institute said.

“Larval zebrafish PDXs were successfully established for all patients and accurately predicted responses to 11 of 12 treatment regimens. For three kids with high-risk cancer, zebrafish models were successfully established where mouse models failed, providing robust and actionable treatment response data that mirrored the actual outcome from each child’s tailored therapy. ”

The CHEO Research Institute adds, “more importantly, this study supports the future use of zebrafish to model the drug responses of pediatric patients with high-risk cancers prospectively and to guide treatment decisions in real time.”

A targeted approach results in fewer side effects, according to Berman.

“For me, it would have meant a specialized treatment. I might not have had as aggressive chemo. I might have had a different treatment plan. Overall. it could. A lot of it’s up in the air, but I would have had options,” says Sarah Telford, a childhood cancer survivor.

Now 27 years old, Telford was diagnosed with AML, Acute Myloid Leukemia, a form of blood cancer at age 11.

“Once I heard the C-word, I knew I was in for a fight.”

Her treatment included multiple rounds of chemo, she says, making her very sick,

“As well as there are a lot of long-term effects that people don’t think about when they think of cancer treatment, for instance, due to treatment,” Telford said. “I am now in a wheelchair, and maybe I wouldn’t be if this had been around.”

“The future with this treatment is so bright.”

• Sign up now for daily CTV News Ottawa newsletters
• The information you need to know, sent directly to you: Download the CTV News App