Single-cell functional and chemosensitive profiling of combinatorial colorectal therapy in zebrafish xenografts

Significance Despite advances in targeted cancer treatments, we still lack methods to predict how a specific cancer will respond to a given therapy. As a consequence, patients go through rounds of trial-and-error approaches based on guidelines to find the best treatment, often subjected to unnecessary toxicity. Using cell lines, we used zebrafish larvae xenografts as sensors for cancer behavior and therapy guideline screening. Our data show not only sufficient resolution to distinguish functional tumor behaviors in just 4 days but also differential sensitivity to colorectal cancer therapy. As proof-of-principle, we provide evidence for similar behavior response to therapies in patients as in zebrafish patient-derived xenografts. Altogether, our results suggest zebrafish larvae xenografts as a promising in vivo screening platform for precision medicine.