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A groundbreaking clinical trial launching this month in Portugal could change the future of cancer treatment, as researchers explore whether zebrafish can help oncologists select the most effective therapy for individual patients. Led by developmental biologist Rita Fior from the Champalimaud Foundation, this five-year study is the first of its kind to assess whether drugs tested on zebrafish embryos implanted with patients’ cancer cells can offer a more personalized treatment approach.
Zebrafish avatars—embryos implanted with human tumor cells—have shown promising results in prior studies. Researchers isolate cancer cells from patients, tag them with fluorescent markers, and transplant them into transparent zebrafish embryos. These fish can then be exposed to different cancer treatments, with researchers observing how the tumors respond to predict which therapies might be most effective for the patient.
Retrospective studies, such as those published in 2017 and 2024, have demonstrated that zebrafish avatars could have accurately predicted chemotherapy outcomes for colorectal cancer patients. In a study involving 55 patients, the avatars correctly forecasted treatment responses for 50 individuals, highlighting their potential in identifying effective therapies and avoiding toxic treatments that could prove futile.
“The ability to predict how therapies will affect a patient’s tumors is crucial,” says Leonard Zon, a stem cell biologist at Harvard Medical School. “If this study demonstrates that zebrafish avatars have high predictive value, it could revolutionize the way oncologists approach cancer treatment.”
Unlike conventional methods that rely on tumor biopsies or blood tests, the zebrafish avatars offer several advantages. They provide results quickly—within just 10 days—and allow researchers to visualize tumor cells in a living organism, where they can better understand how cancer cells interact with the body. This level of detail may offer oncologists a clearer picture of how treatments could work or fail.
Moreover, zebrafish avatars are less expensive to maintain than mouse models and faster than growing cancer cells in culture. The embryos also offer a unique opportunity to observe cancer’s progression and potential for metastasis, critical information in choosing the right treatment.
The upcoming trial will involve patients with metastatic breast or ovarian cancer. Researchers will extract tumor cells from the fluid typically drained from patients’ abdomens during treatment and implant those cells into the zebrafish embryos. While many clinical trials focus on experimental drugs, this study will test a combination of approved treatments to determine the most effective regimen based on the fish’s response.
Despite the promising data, zebrafish avatars face resistance from some oncologists. “Clinicians are still hesitant to embrace this approach,” says molecular geneticist Kathleen Claes. “But if this trial can show the added value, it could have a transformative impact on treating patients with unclear treatment options.”
Richard White, a cancer biologist and oncologist at the University of Oxford, agrees. “Oncologists are data-driven. If you give them solid data, they will embrace it,” he says, highlighting the potential of zebrafish avatars to become a standard tool in the fight against cancer.
As the trial unfolds, the scientific community will be watching closely to determine whether zebrafish avatars can offer a more reliable and personalized alternative to the current trial-and-error approach in cancer treatment. If successful, this method could herald a new era of faster, more precise treatments, saving time and potentially improving outcomes for cancer patients worldwide.
