Precision medicine in ovarian cancer by zebrafish patient-derived xenograft systems

Purpose and goal

We successfully implanted patient-derived tumor material into zebrafish embryos (Zeb-PDX), and to use these for evaluating drug response rates, using material from in total 28 patients with ovarian-, bladder- or colorectal-cancer. We established that these methods work even if the tumor tissue was shipped from Spain, and also if it was first cryopreserved and then thawed prior to implantation. This means that we in the future can establish Zeb-PDX models from cancer patients all over the world.

Expected results and effects

Millions of living tumor cells were isolated from in total 43 biopsies and implanted in hundreds of zebrafish embryos. Five different treatment were evaluated using 9 biopsies, and the results were similar to those obtained using mouse-PDX models or seen in the patients themselves. We also developed and validated analysis software and established contacts with clinics, investors, companies, patient organizations, and others leading to a clear go-to-market plan for the Zeb-PDX Product.

Planned approach and implementation

By focusing on ovarian cancer, we were able to establish the techniques on a large patient material. We discovered that ovarian cancer is a more heterogeneous disease than anticipated, and that additional research is needed for this tumor type. We also evaluated the method for bladder cancer where less heterogeneity was observed and a faster clinical application was envisioned. Our market analysis demonstrated a strong interest in the Zeb-PDX system from clinics, patients and companies.