Patient-derived xenograft in zebrafish embryos: a new platform for translational research in gastric cancer

Wu, Jiaqi; Zhai, Jing; Li, Chong-Yong; Tan, Aimin; Wei, Ping; Shen, Lizong; He, Ming-Fang

doi:10.1186/s13046-017-0631-0

Cited by 80 publications

(89 citation statements)

References 44 publications

(51 reference statements)

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“…Regarding zebrafish larval xenografts using patient-derived samples, few studies have been published so far (see Table S1). Nevertheless, these studies show promising results and the reliability of the zPDX model to establish different cancer types, as it is able to overcome some of the disadvantages of the murine PDXs such as the time required to develop an assay, as well as number of cells needed for implantation [106,115,[128][129][130][131].…”

Section: Zebrafish Patient-derived (Zpdx)-avatarsmentioning

confidence: 99%

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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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Section: Zebrafish Patient-derived (Zpdx)-avatarsmentioning

confidence: 99%

“…Subsequent work from Wu J.Q. et al [129] showed that patient-derived gastric zPDXs were able to metastasize and recruit vessels into the tumor mass. A retrospective correlation with the patient clinical outcome was shown only for one patient.…”

Section: Zebrafish Patient-derived (Zpdx)-avatarsmentioning

confidence: 99%

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

Costa

Estrada

Mendes

et al. 2020

Cells

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“…Upon localised or haematogenous engraftment of cancer cells, zebrafish xenografts allow qualitative and quantitative assessment of tumour burden and tumour-microenvironment interaction, representing a powerful pre-clinical model to unravel cancer mechanisms and to develop new therapeutic strategies [61] . In particular, alongside murine models, the use of PDXs in zebrafish has the potential to be used in personalised medicine [63][64][65][66] , with the advantage of requiring less tumour material and shorter times for the monitoring of tumour development [57] . Several studies have shown that the combined use of zebrafish and murine models paves the way towards important insights to elucidate the biology of metastatic cancers and the development of new treatments [67][68][69][70][71] .…”

Section: Zebrafish Xenograft As a Model To Study Cancermentioning

confidence: 99%

CXCR4 signalling, metastasis and immunotherapy: zebrafish xenograft model as translational tool for anti-cancer discovery

Tulotta¹,

Snaar-Jagalska²

2019

JCMT

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Cell-to-cell communication guarantees homeostasis in a multi-cellular organism. Cancer-to-microenvironment communication sustains malignant growth and dissemination. Whereas the accumulation of mutations is at the origin of malignant cell transformation and neoplasia onset, the interaction between cancer and the surrounding stroma, specifically immune cells, influences the balance between tumour regression and tumour progression. To study how the interaction between cancer and stromal cells is disadvantageous or beneficial for tumour progression, the use of a transparent in vivo model bears important research potentials. Zebrafish has been increasingly used as animal model to study tumour biology. The use of transparent zebrafish embryos, with fluorescent endothelial and immune cells, allows the visualization of cell-to-cell interaction, among host cells themselves and between zebrafish stroma and implanted human cancer cells. Here, we summarise our findings on the role of CXCR4 signalling in tumour progression, considering its signature both on cell autonomous and host dependent mechanisms. Finally, we address the translational impact of targeting CXCR4 signalling in cancer and the tumour microenvironment for the treatment of metastatic cancer.

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“…xenograft (zPDX) models have also been generated by transplanting hundreds of cells from human tumor tissue with a high success rate [3,[5][6][7][8]. The relative stemness and immature immune environment of zebrafish larvae represent proper conditions for the growth of human cancer cells [9].…”

Section: Introductionmentioning

confidence: 99%

“…Compared with the mouse xenograft model, the transparent zebrafish larvae xenograft model offers the speed and intuitiveness for studies on the cellular resolution level with relatively large samples [1,7,8], which would contribute to the study of tumor biology. Thus, developing reliable zebrafish…”

mentioning

confidence: 99%

Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion

Shen

Sun

et al. 2020

Preprint

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Background: Numerous studies have shown that long noncoding RNAs play important roles in human cancer progression. Although zebrafish xenografts have recently become a novel in vivo model for human cancer research, whether such models can be used to study the function of long noncoding RNAs remains unknown. Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies of zebrafish xenografts also confirmed these roles of LINC00152. In vivo confocal imaging was used to more accurately evaluate the function of LINC00152 in cell proliferation and migration. Pharmacological experiments were further performed to study the potential ability of LINC00152 downregulation combined with an EGFR inhibitor to treat tumors in cultured cells and the zebrafish xenograft model. Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro . In the zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells, as indicated by the two imaging methods at different magnifications. Moreover, the knockdown of LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and the zebrafish xenograft model. Conclusion: Our study reveals the oncogenic roles and potential for LINC00152 to be a target for tumor treatment in lung cancer using zebrafish xenograft models, and the findings suggest that this model could be used for functional and application studies of human long noncoding RNAs in tumor biology.

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Patient-derived xenograft in zebrafish embryos: a new platform for translational research in gastric cancer

Cited by 80 publications

References 44 publications

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

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

CXCR4 signalling, metastasis and immunotherapy: zebrafish xenograft model as translational tool for anti-cancer discovery

Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion

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