Zebrafish against cancer: towards clinical relevance

Most cancer therapeutics that show preclinical promise fail in clinical trials, underscoring the need for complementary disease models. Over the past two decades, zebrafish models have matured from a tool for studying vertebrate development into a versatile platform spanning the translational cancer pipeline. Transgenic and transplantation zebrafish models have dissected fundamental mechanisms of tumor initiation and metastasis. Beyond mechanistic insight, phenotypic chemical and genetic screens provide a rapid, whole-organism filter to prioritize and repurpose therapeutic candidates, several of which have reached the clinic. Most recently, zebrafish patient-derived xenografts have begun to predict individual patient treatment responses within clinically actionable timeframes. Tracing this evolution, we argue that zebrafish models are not a replacement for other systems but earn their translational value when applied to the questions they answer best and when embedded in co-clinical workflows alongside oncology teams.