Quo natas, Danio?—Recent Progress in Modeling Cancer in Zebrafish

Kirchberger, Stefanie; Sturtzel, Caterina; Pascoal, Susana; Distel, Martin

doi:10.3389/fonc.2017.00186

Cited by 59 publications

(54 citation statements)

References 141 publications

(142 reference statements)

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“…The zebrafish is an excellent model for in vivo investigation of disease mechanisms relevant to human disease including cancers and can also serve as a platform for the screening of therapeutic drugs [15] , [39] . Several previous studies in zebrafish cancer models in the brain [40] , liver [20] , [26] , [27] , [28] , and pancreas [41] have demonstrated that continued kras V12 expression is required for tumor maintenance.…”

Section: Discussionmentioning

confidence: 99%

Inducible Intestine-Specific Expression of kras Triggers Intestinal Tumorigenesis In Transgenic Zebrafish

Raghuram

Fong

et al. 2018

Neoplasia

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KRAS mutations are a major risk factor in colorectal cancers. In particular, a point mutation of KRAS of amino acid 12, such as KRASV12, renders it stable activity in oncogenesis. We found that krasV12 promotes intestinal carcinogenesis by generating a transgenic zebrafish line with inducible krasV12 expression in the intestine, Tg(ifabp:EGFP-krasV12). The transgenic fish generated exhibited significant increases in the rates of intestinal epithelial outgrowth, proliferation, and cross talk in the active Ras signaling pathway involving in epithelial-mesenchymal transition (EMT). These results provide in vivo evidence of Ras pathway activation via krasV12 overexpression. Long-term transgenic expression of krasV12 resulted in enteritis, epithelial hyperplasia, and tubular adenoma in adult fish. This was accompanied by increased levels of the signaling proteins p-Erk and p-Akt and by downregulation of the EMT marker E-cadherin. Furthermore, we also observed a synergistic effect of krasV12 expression and dextran sodium sulfate treatment to enhance intestinal tumor in zebrafish. Our results demonstrate that krasV12 overexpression induces intestinal tumorigenesis in zebrafish, which mimics intestinal tumor formation in humans. Thus, our transgenic zebrafish may provide a valuable in vivo platform that can be used to investigate tumor initiation and anticancer drugs for gastrointestinal cancers.

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Section: Discussionmentioning

confidence: 99%

Inducible Intestine-Specific Expression of kras Triggers Intestinal Tumorigenesis In Transgenic Zebrafish

Raghuram

Fong

et al. 2018

Neoplasia

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“…To date, an extensive list of improved zebrafish cancer models has been reported, including models to study neuroblastoma, brain cancer, eye cancer, leukemia, melanoma, uveal melanoma, and liver cancer, among others [ 177 ]. More complex models to study the mechanisms of tumor cell dissemination and metastases formation have also been reported [ 178 , 179 ].…”

Section: The Potential Of Zebrafish For Increasing the Translationmentioning

confidence: 99%

The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines

Gutiérrez-Lovera

Vázquez-Ríos

Guerra‐Varela

et al. 2017

Genes

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In the last few decades, the field of nanomedicine applied to cancer has revolutionized cancer treatment: several nanoformulations have already reached the market and are routinely being used in the clinical practice. In the case of genetic nanomedicines, i.e., designed to deliver gene therapies to cancer cells for therapeutic purposes, advances have been less impressive. This is because of the many barriers that limit the access of the therapeutic nucleic acids to their target site, and the lack of models that would allow for an improvement in the understanding of how nanocarriers can be tailored to overcome them. Zebrafish has important advantages as a model species for the study of anticancer therapies, and have a lot to offer regarding the rational development of efficient delivery of genetic nanomedicines, and hence increasing the chances of their successful translation. This review aims to provide an overview of the recent advances in the development of genetic anticancer nanomedicines, and of the zebrafish models that stand as promising tools to shed light on their mechanisms of action and overall potential in oncology.

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“…The zebrafish genome is sequenced, sharing 70% of homology with humans, namely in crucial pathways involved in vertebrate development and cancer. It is also reported that 82% of disease-causing human proteins have an ortholog in zebrafish [101].…”

Section: Zebrafish Xenograftsmentioning

confidence: 99%

Zebrafish Avatars towards Personalized Medicine—A Comparative Review between Avatar Models

Costa

Estrada

Mendes

et al. 2020

Cells

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Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored according to average response rates. "Omics" approaches are used for patient stratification and choice of therapeutic options towards a more precise medicine. These methods, however, do not consider all genetic and non-genetic dynamic interactions that occur upon drug treatment. Therefore, the need to directly challenge patient cells in a personalized manner remains. The present review addresses the state of the art of patient-derived in vitro and in vivo models, from organoids to mouse and zebrafish Avatars. The predictive power of each model based on the retrospective correlation with the patient clinical outcome will be considered. Finally, the review is focused on the emerging zebrafish Avatars and their unique characteristics allowing a fast analysis of local and systemic effects of drug treatments at the single-cell level. We also address the technical challenges that the field has yet to overcome.The arrival of precision medicine and immunotherapy are giving hope to finally manage cancer treatment. Many advances were made possible due to the discovery of molecular pathways in tumor cells and on their interaction with the surrounding tumor microenvironment (TME) [1], leading to the development of many new therapies. The latest successes in HER2-targeted therapy and the discovery of immune checkpoint inhibitors are great examples of this [2]. However, not all patients respond and many are not eligible for these "new therapies". Thus, nowadays, the majority of patients are still treated with traditional chemo/radiotherapy and surgery according to clinical guidelines, which are developed and approved based on average efficacy rates.As a result of this "one-size-fits-all" approach, treatments may prove to be efficient for some patients but not for others. For example, in the international therapeutic guidelines (NCCN and ESMO) for advanced colorectal cancer (CRC) there are two main chemotherapeutic arms (FOLFOX and FOLFIRI), which show very similar response rates of~50% [3,4]. In other words,~50% of patients respond to treatment while~50% do not. Clinicians do not know in which group patients will fall, as there is no predictive screening test to provide this information. Thus, patients that start with FOLFOX and do not respond change to FOLFIRI, and vice-versa. This applies for CRC and many other cancers, being especially relevant in the metastatic scenario when oncology therapy guidelines reach branch

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Quo natas, Danio?—Recent Progress in Modeling Cancer in Zebrafish

Cited by 59 publications

References 141 publications

Inducible Intestine-Specific Expression of kras Triggers Intestinal Tumorigenesis In Transgenic Zebrafish

Inducible Intestine-Specific Expression of kras Triggers Intestinal Tumorigenesis In Transgenic Zebrafish

The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines

Zebrafish Avatars towards Personalized Medicine—A Comparative Review between Avatar Models

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