Estrada, Marta F.Amorim, FilipaSilva, Filipa Ferreira daAlmeida, Cátia Rebelo deFontes, MárciaCoelho, RicardoFerreira, SóniaCanas-Marques, RitaCastillo-Martin, MireiaCasanova, JoãoBatarda, Maria de LurdesYaniz-Galende, ElisaLeFormal, AudreyMarreiros, AnaJacob, FrancisHeinzelmann-Schwarz, ViolaLeary, AlexandraNabais, HenriqueFior, Rita2026-03-052026-03-052026-012666-3791http://hdl.handle.net/10400.1/28342In ovarian cancer, 80% of patients relapse after first-line therapy. In recurrent cases, oncologists lack reliable tests to guide chemotherapy choices, creating an unmet clinical need. Here, we develop the ovarian cancer zebrafish Avatar-test, a functional in vivo model using patient tumor cells implanted in zebrafish embryos to predict treatment responses. We present the largest observational study (32 patients), where the zAvatar-test achieves 91% accuracy in predicting patient outcomes. Patients with a zAvatar-sensitive-test correlate with longer progression-free survival (17 vs. 6 months). Tumors in zAvatars are dynamic, with human-host cell interactions, and higher metastatic potential in poor-prognosis cases. Finally, as a proof of concept, we demonstrate that venetoclax has the potential to sensitize multidrug-resistant tumors. Altogether, this clinical study demonstrates that the zAvatar-test may help clinicians personalize treatments for ovarian cancer patients. We are now conducting a multicentric randomized clinical trial to evaluate the zAvatar-test as a companion tool in clinical oncology.engjournal article10.1016/j.xcrm.2025.102530