Fish will assist oncologists in making more effective decisions regarding cancer treatment.

A five-year study led by biologist Rita Fior from the Champalimaud Foundation will be the first randomized trial in which patients receive medications previously tested on zebrafish embryos implanted with cancer cells from the patients. Retrospective studies have shown that so-called avatars (personalized models) of fish could identify successful treatment methods if created in advance, and now Fior and her colleagues aim to determine how beneficial this approach can be for patients.

There are already numerous other cancer avatars: mice, fruit flies, and cell cultures—all designed to serve as personalized testing systems to determine how therapies will affect patients' tumors, but each has its limitations.

Differences in patients' tumors—genetics, metabolism, and growth potential—can make choosing the right cancer treatment a challenging task for oncologists. As multiple nearly equivalent options may be available, patients often undergo one harmful therapy after another to find the one that works. Sometimes genomic analysis helps in making the right choice, but even if a patient's cancer carries mutations indicating a specific treatment option, there is no guarantee that the patient will respond to the therapy.

In search of a better alternative, Fior's laboratory has been studying zebrafish avatars for nearly a decade. Researchers extract cancer cells from the patient, label them with fluorescent markers in the lab, and transplant them into transparent zebrafish embryos that naturally grow outside the mother's body. Researchers can add cancer drugs or apply radiation to the water where the fish live and then observe the fluorescent tumor cells to determine whether the patient's tumor will respond to such treatment. Equally important, by demonstrating options that will not work, avatars can spare patients from potentially toxic and ultimately ineffective treatments.

In a report published in the journal Nature Communications, scientists described the creation of zebrafish avatars for a group of 55 patients and assigned the same type of chemotherapy to the fish that the patients received. For 50 of the patients, the fish accurately "predicted" the treatment outcome. An additional advantage is that avatars can reveal key characteristics of tumors, such as the likelihood of metastasis.

Proponents of zebrafish argue that their avatars possess a unique combination of benefits. Like cell cultures, they provide rapid results—within 10 days—an important timeframe for making clinical decisions.

Zebrafish are more similar to humans than cell cultures, and their cultivation is much cheaper than breeding mice. The small transparent embryos are easier to analyze. One can examine the entire animal under a microscope and easily locate metastases in its tissues.

When it comes to recognition from oncologists, zebrafish avatars are still "swimming against the current." Doctors are still somewhat resistant to working with fish, but this research could be groundbreaking if it proves additional value for that group of patients for whom further options are unclear.