Title: Zebrafish Avatar-Test Forecasts Clinical Response to Chemotherapy in Patients with Colorectal Cancer

Authors: Bruna Costa, Marta F. Estrada, António Gomes, Laura M. Fernandez, José M. Azevedo, Vanda Póvoa, Márcia Fontes, António Alves, António Galzerano, Mireia Castillo-Martin, Ignacio Herrando, Shermann Brandão, Carla Carneiro, Vítor Nunes, Carlos Carvalho, Amjad Parvaiz, Ana Marreiros, and Rita Fior 

Journal: Nature Communications

Year: 2024

Header image adapted from Unsplash.com

Chemotherapies play an important role in controlling tumor metastasis and preventing relapse after tumor excision. However, one of the biggest challenges faced in cancer treatment is choosing the most effective chemotherapy for a given patient. This is because many factors including genetics, metabolism, cancer stage, as well as tumor heterogeneity and growth potential influence how a patient’s cancer will respond to treatment. The current tools clinicians use to choose a medication (including genetic testing) can be expensive and have limited predictive power due to all these contributing factors. Thus, it is difficult for oncologists to predict a patient’s clinical response prior to drug administration. As a result, patients often undergo a series of trial-and-error tests to pinpoint the best treatment. Now, developmental biologist Rita Fior and colleagues at the Champalimaud Foundation in Portugal are trying to change that by giving clinicians a leg up in therapeutic decision-making. By prescribing the most effective medication first, patients would avoid the burden of unnecessary side effects from the ineffective chemotherapies, and they’ll receive the treatment they need quicker.

Fior’s clinical study was published in June 2024 in Nature Communications and leverages the use of zebrafish to screen for personalized cancer treatments. The team focused on colorectal cancer (CRC) which is the third most common type of cancer diagnosed worldwide. First, the scientists isolated CRC cells from patients and tagged them with fluorescent markers. Next, they injected these cells into zebrafish embryos which then served as models for each patient’s cancer. After treating the zebrafish with radiation or cancer drugs, the scientists could analyze how the tumors were affected and use this information to predict how the corresponding patients would respond to the same treatments. Figure 1 shows a fluorescently-labelled zebrafish containing cancer cells from a patient.

After measuring how the cancer in the zebrafish responded to the treatments using fluorescence microscopy, the scientists found that this “zAvatars” test gave an impressive value of ~91% accuracy across a pool of 55 CRC patients. In other words, for 50 of the patients, the fish model accurately predicted the outcome of the treatments used. Furthermore, the test renders a quick turnaround time, taking only 10 days to obtain the results.

Other model organisms have been used in the past to help predict personalized cancer treatments.  However, they have shortcomings. For example, mouse models simply take too long to yield results. Cell cultures have also been used wherein patient cancer cells are grown in a dish, but such techniques don’t mimic the complex and dynamic environment of a living organism. Zebrafish offer unique advantages because they’re inexpensive and allow for results to be obtained quickly. They’re also small and transparent which enables scientists to easily visualize the entire organism using fluorescent microscopy. By doing so, scientists can see whether the cancer spread to other areas in the zebrafish such as the tail and the eyes.

Overall, the researchers successfully developed a screening platform to predict how well a patient’s cancer will respond to chemotherapy drugs. The research team is already preparing for a 5-year randomized clinical trial to further demonstrate the clinical benefit of this zAvatar-test. Set to begin in January 2025, the trial will compare the best therapy as predicted by the zAvatar test with the therapy chosen by the physician who doesn’t have any knowledge of the test results. Hopefully, we’ll see the zAvatar test enter the clinic on a larger scale and be applied to different types of cancer, enabling physicians to more quickly prescribe effective cancer treatments for their patients.

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This is an unofficial adaptation of an article that appeared in an Open Access Nature Communications publication. Nature Portfolio has not endorsed the content of this adaptation or the context of its use.

Figures are reprinted or adapted with permission from Costa et al. Copyright 2024 Nature Communications.

Full Reference: Costa, B., Estrada, M.F., Gomes, A. et al. Zebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancer. Nat Commun 15, 4771 (2024). https://doi.org/10.1038/s41467-024-49051-0