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Oncology is one of the areas of interest of our ZeClinics’ research and development program. As a result, we have recently validated a cell line derived xenograft (CDX) model in zebrafish embryos, aimed at supporting biopharma’s cancer research or anti-tumor drug development.
Despite their translational value, the high cost and low throughput of mouse models hamper their use for screening large numbers of possible therapies. Therefore, the use of innovative screening systems, including alternative model organisms, could reduce costs and time and allow for assessing more compounds. This would indeed increase the chances of success in clinical trials and, hence, reduce drug attrition rates.
In this context, zebrafish larvae are positioned as a valuable alternative to overcome these restrictions. Fewer cells and drug amounts are needed, their transparency allows direct in vivo observation, and there is no need for immuno-compromised animals. In addition, zebrafish larvae provide biologically-relevant readouts, since many of the mechanisms of tumor production are shared by zebrafish and humans:
Cell proliferation for cancer progressionEpigenetics, such as tumor suppressor gene silencingDifferentiation, like oncogene transdifferentiationCell signaling pathways, such as Fibroblast Growth Factor (FGF)Neural crest cell derivatives, involved in melanomaIntersegmental vessels (ISV) morphology, related to angiogenesisHematopoiesis processes, involved in leukemia
Cell proliferation for cancer progression
Epigenetics, such as tumor suppressor gene silencing
Differentiation, like oncogene transdifferentiation
Cell signaling pathways, such as Fibroblast Growth Factor (FGF)
Neural crest cell derivatives, involved in melanoma
Intersegmental vessels (ISV) morphology, related to angiogenesis
Hematopoiesis processes, involved in leukemia
Our optimized model offers other advantages including real volume observation (no estimations), high sensitivity with possibility to look at micrometastasis, and automated measurements of initial proliferation and metastatic events, which allow high throughput screening.
Moreover, individual cancer genotype is emerging as a crucial factor leading therapeutic decisions. We are currently working to adapt our model set up to a patient derived xenograft (PDX) model in the future. Due to the high amount of tissue needed for transplants in PDXs rodent models, it would represent an alternative solution.