Patient-derived Heterogeneous Xenograft Model of Pancreatic Cancer Using Zebrafish Larvae as Hosts for Comparative Drug Assessment

Wang, Lei; Chen, Huan; Fei, Fei; He, Xianfeng; Sun, Song; Lv, Kunpeng; Yu, Bo; Jiang, Long; Wang, Xu

doi:10.3791/59507

Cited by 18 publications

(26 citation statements)

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“…An alternative approach to direct injection of patient cells is to expand tumor cells in vitro before injection, with the possibility of introducing genetic modifications. This approach was recently described by Wang et al [132], where in addition to the dual labelling of tumor cells and fibroblasts with fluorescent reporters, the anti-apoptotic gene BCL2L1 was also overexpressed to prolong the life span of the xenografted cells. The zebrafish used were also humanized to express insulin and insulin growth factor-1 to better support survival and proliferation of implanted human cells.…”

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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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%

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

Costa

Estrada

Mendes

et al. 2020

Cells

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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…”

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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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“…Conclusion: Our study reveals the oncogenic roles and potential tumor treatment target of LINC00152 in lung cancer cells by zebrafish xenograft models, suggesting that this model could be used for the functional and application study of human lncRNA in tumor biology. model was also generated by transplanting hundreds of cells from human tumor tissue with high success rate [3,[5][6][7][8]. It seems that the relative stemness and immature immune environment of zebrafish larvae is very proper for the growth of human cancer cells [9].…”

mentioning

confidence: 99%

“…It seems that the relative stemness and immature immune environment of zebrafish larvae is very proper for the growth of human cancer cells [9]. Compared with the xenograft in nude mouse, transparent zebrafish larvae xenograft offers the speed and intuitive studies on cellular resolution level with a relatively large samples [1, 7,8], which will benefit the study of tumor biology. Thereafter, developing the reliable zebrafish xenograft becomes more and more important for tumor biology in basic research and personalized clinical test.…”

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 show that long non-coding RNAs take important roles in human cancer progression. Although zebrafish xenograft become a novel in vivo model for human cancer research recently, whether it can be used for studying the function of lncRNAs remains unknown.Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies by using zebrafish xenograft also confirmed these roles of LINC00152. In vivo confocal imaging was also used to evaluate the function of LINC00152 in cell proliferation and migration more accurately. Pharmacology experiments were further performed to study the potential tumor treatment of LINC00152 downregulation combined with EGFR inhibitor in cultured cells and zebrafish xenograft.Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro . In zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells by two imaging methods at different magnification. Moreover, knocking-down LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and zebrafish xenograft model.Conclusion: Our study reveals the oncogenic roles and potential tumor treatment target of LINC00152 in lung cancer cells by zebrafish xenograft models, suggesting that this model could be used for the functional and application study of human lncRNA in tumor biology.* Wenyi Shen and Juan Pu contributed equally to this work.

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Patient-derived Heterogeneous Xenograft Model of Pancreatic Cancer Using Zebrafish Larvae as Hosts for Comparative Drug Assessment

Cited by 18 publications

References 0 publications

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

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

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

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

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