title: Zebrafish xenograft models of cancer and metastasis for drug discovery.
abstract: Patients with metastatic cancer suffer the highest rate of cancer-related death, but existing animal models of metastasis have disadvantages that limit our ability to understand this process. The zebrafish is increasingly used for cancer modelling, particularly xenografting of human cancer cell lines, and drug discovery, and may provide novel scientific and therapeutic insights. However, this model system remains underexploited. Areas covered: The authors discuss the advantages and disadvantages of the zebrafish xenograft model for the study of cancer, metastasis and drug discovery. They summarise previous work investigating the metastatic cascade, such as tumour-induced angiogenesis, intravasation, extravasation, dissemination and homing, invasion at secondary sites, assessing metastatic potential and evaluation of cancer stem cells in zebrafish. Expert opinion: The practical advantages of zebrafish for basic biological study and drug discovery are indisputable. However, their ability to sufficiently reproduce and predict the behaviour of human cancer and metastasis remains unproven. For this to be resolved, novel mechanisms must to be discovered in zebrafish that are subsequently validated in humans, and for therapeutic interventions that modulate cancer favourably in zebrafish to successfully translate to human clinical studies. In the meantime, more work is required to establish the most informative methods in zebrafish.
authors.affiliation: a Department of Oncology and Metabolism , The Medical School, University of Sheffield , Sheffield , UK.|b Sarcoma Research Unit, Medical School , INSERM, European Associated Laboratory, University of Sheffield , Sheffield , UK.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Brown
authors.affiliation: a Department of Oncology and Metabolism , The Medical School, University of Sheffield , Sheffield , UK.|b Sarcoma Research Unit, Medical School , INSERM, European Associated Laboratory, University of Sheffield , Sheffield , UK.
authors.forename: Kristina
authors.initials: K
authors.lastname: Schiavone
authors.affiliation: a Department of Oncology and Metabolism , The Medical School, University of Sheffield , Sheffield , UK.|c The Bateson Centre for Lifecourse Biology , University of Sheffield, Western Bank , Sheffield , UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Tazzyman
authors.affiliation: a Department of Oncology and Metabolism , The Medical School, University of Sheffield , Sheffield , UK.|b Sarcoma Research Unit, Medical School , INSERM, European Associated Laboratory, University of Sheffield , Sheffield , UK.|d UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours , Nantes University Hospital , Nantes , France.|e Faculty of Medicine , INSERM, UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Equipe Ligue 2012, University of Nantes , Nantes , France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.affiliation: c The Bateson Centre for Lifecourse Biology , University of Sheffield, Western Bank , Sheffield , UK.|f Department of Infection, Immunity & Cardiovascular Disease , The Medical School, University of Sheffield , Sheffield , UK .
authors.forename: Timothy Ja
authors.initials: TJ
authors.lastname: Chico
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000473:pathology; D013045:Species Specificity; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; metastasis; xenotransplantation; zebrafish