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    Systematic Roadmap for Cancer Drug Screening Using Zebrafish Embryo Xenograft Cancer Models: Melanoma Cell Line as a Case Study

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    Authors
    Letrado, Patricia; email: patricia.letrado@ikanbiotech.com
    Mole, Holly; email: holly.mole@manchester.ac.uk
    Montoya, María; email: mmontoya68@gmail.com
    Palacios, Irene; email: irene.palacios@cnic.es
    Barriuso, Jorge; orcid: 0000-0002-5641-9105; email: jorge.barriuso@manchester.ac.uk
    Hurlstone, Adam; orcid: 0000-0001-5260-9457; email: adam.hurlstone@manchester.ac.uk
    Díez-Martínez, Roberto; email: roberto.diez@ikanbiotech.com
    Oyarzabal, Julen; email: julenoyarzabal@external.unav.es
    Publication Date
    2021-07-23
    
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    Abstract
    Zebrafish embryo tumor transplant models are widely utilized in cancer research. Compared with traditional murine models, the small size and transparency of zebrafish embryos combined with large clutch sizes that increase statistical power and cheap husbandry make them a cost-effective and versatile tool for in vivo drug discovery. However, the lack of a comprehensive analysis of key factors impacting the successful use of these models impedes the establishment of basic guidelines for systematic screening campaigns. Thus, we explored the following crucial factors: (i) user-independent inclusion criteria, focusing on sample homogeneity; (ii) metric definition for data analysis; (iii) tumor engraftment criteria; (iv) image analysis versus quantification of human cancer cells using qPCR (RNA and gDNA); (v) tumor implantation sites; (vi) compound distribution (intratumoral administration versus alternative inoculation sites); and (vii) efficacy (intratumoral microinjection versus compound solution in media). Based on these analyses and corresponding assessments, we propose the first roadmap for systematic drug discovery screening in zebrafish xenograft cancer models using a melanoma cell line as a case study. This study aims to help the wider cancer research community to consider the adoption of this versatile model for cancer drug screening projects.
    Citation
    Cancers, volume 13, issue 15, page e3705
    Publisher
    MDPI
    URI
    http://hdl.handle.net/10034/625372
    Type
    article
    Description
    From MDPI via Jisc Publications Router
    History: accepted 2021-07-19, pub-electronic 2021-07-23
    Publication status: Published
    Funder: Gobierno de Navarra; Grant(s): 0011-1408-2016-000004, 0011-1365-2020-000292
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