A zebrafish colorectal xenograft model for chemotherapy response

Colorectal cancer (CRC) is the third most diagnosed cancer globally and the third leading cause of cancer-related deaths. Early-stage CRC treatment consists of a combination of surgery, radiotherapy, and chemotherapy, while advanced CRC remains difficult to manage, most patients will experience disease progression and require multiple lines of systemic therapy. Choosing the right therapy is often a challenge since most chemotherapeutics lack distinctive biomarkers, thus functional testing has emerged as a promising strategy to personalize therapy and minimize unnecessary toxicity. In this study, we present our zebrafish (Danio rerio) xenograft model to evaluate the response to first-line chemotherapeutic protocols commonly used in clinical practice. We demonstrate that after a short course of chemotherapy there is an evident reduction in primary tumor size, circulating tumor cells, and metastasis area during the follow-up period. These changes were more pronounced in subgroups treated with Irinotecan, indicating the xenografts sensitivity to these protocols. We believe this model has significant potential for both fundamental cancer research and translational applications.