Zebrafish Avatars, towards personalised medicine

Despite advances in targeted cancer treatments, we still lack methods to predict how a specific cancer in a specific patient will respond to a given therapy. Consequently, patients go through rounds-of-trial-and-error approaches based on guidelines to find the best treatment, often subjected to unnecessary toxicity. We are developing zebrafish-larvae-xenografts as sensors for cancer behavior and personalized therapy screening. The test is based on the injection of tumor cells from patients into zebrafish larvae to then test which is the best therapy for that particular patient, within the available approved therapeutic options. Our data not only shows sufficient resolution to distinguish functional tumor behaviors in just 4-days, but also differential sensitivity to colorectal cancer therapies. As proof-of-principle experiments, in this study we provide evidence for a similar response to therapy in patients and their corresponding Zebrafish Avatars. Now we have recently expanded our assay to screen also Radiotherapy response (Costa et al, Ebiomedicine 2019).
Altogether, our results suggest zebrafish-larvae-xenografts as a promising in vivo screening platform for personalised medicine (Fior et al, PNAS 2017, Costa et al, Ebiomedicine 2019).

In collaboration with Champalimaud Clinical Centre and the Hospital Amadora Sintra, we have started 2 clinical studies: one in CRC and another in Breast cancer, to test the predictiveness of this assay by comparing the therapeutic response obtained in patients with its matching zebrafish PDX/ Avatars in many patients to further validate the model.

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