Rita Fior, head of the Cancer Development and Innate Immune Evasion Group at the Champalimaud Foundation (CF), has been investigating for several years the ability of zebrafish avatars, or zAvatars, of cancer patients to guide therapeutic decisions. The goal: to predict individual cancer treatment outcomes, thereby enabling the selection of the best available chemotherapy for each patient.
The idea behind zAvatars is quite straightforward, involving taking the tumor cells of each patient and injecting them into zebrafish embryos, effectively turning these embryos into “avatars” of the respective cancer patient. Subsequently, the different treatment options available for the patient can be applied to the zAvatars to select the best one. This approach has the advantage of providing faster results – within days rather than months or several weeks – than the traditional mouse model or even tumor organoids.
In 2017, Fior and a multidisciplinary team of colleagues from CF and other institutions conducted a proof-of-concept study, showing that the zAvatar method is indeed a viable and promising model ( http://magazine.ar.fchampalimaud.org/zebrafish-larvae-could-be-used-as-avatars-for-the-personalized-treatment-of-cancer/ ).
In a much larger clinical study involving 55 patients with colorectal cancer (CRC) from the Champalimaud Clinical Centre and the Fernando Fonseca Hospital, published today (June 5, 2024) in the journal Nature Communications, Fior’s team and colleagues have now developed a so-called “zAvatar test”. And they conclude that the test can predict a patient’s response to a specific chemotherapy with 91% accuracy.
To create the avatars, researchers inject patients’ tumor cells directly into the zebrafish embryos, thus generating the zAvatars. They then test the different chemotherapies on these tumors, comparing the zAvatars’ response to the patient’s actual response to the same chemotherapy. In this way, they have now been able to successfully predict the clinical outcomes of 50 out of the 55 patients.
The team’s statistical analysis revealed that three variables are the most important factors for predicting patient response to treatment based on zAvatars. These are the patient’s tumor stage, as well as the increase in cell death (“apoptosis fold-change”) and the tumor’s metastasis potential in the zAvatars.
"This shows that treating the right patient with the right treatment has the potential to really improve the patient’s prognosis. And that is our goal: to have a test that helps to guide and optimize clinical decisions in a truly personalized way," says Rita Fior.
