Zebrafish Xenotransplant Cancer Model for Drug Screening - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 211

Chapter 17

Zebrafish Xenotransplant
Cancer Model for Drug
Screening

Chunqi Li, Liqing Luo, and Patricia McGrath
Phylonix, Cambridge, MA, USA

17.1 INTRODUCTION

Although immunodeficient mice have played an important role in cancer research,
new cost-effective xenotransplant (Xt) animal models are needed to improve pre-
clinical drug discovery and screening. In this research, we describe methods for
developing a zebrafish xenotransplant cancer model and a whole animal ELISA for
drug screening. For model development, we microinjected human colon cancer cells
into 3 days post fertilization (dpf) zebrafish and assessed proliferation, migration, and
mass formation. Next, using a human cell-specific antibody that exhibited limited
cross-reactivity with zebrafish tissues, we developed a quantitative microplate-based
whole zebrafish ELISA. Xenotransplant zebrafish were then treated with four FDA-
approved cancer drugs (5-fluorouracil (5-FU), oxaliplatin, camptothecin, and leu-
covorin) and one drug combination (5-fluorouracil leucovorin) and results for four

of the five drugs and the drug combination were similar to results in humans.

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17.2 BACKGROUND AND SIGNIFICANCE

17.2.1 Conventional Mouse Xenograft Models

Quantitating cancer cells in vivo to assess drug efficacy is a major challenge.
Although mice remain the model system of choice for cell transplantation
(Kelland, 2004), there are several inherent disadvantages associated with mouse