Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish

Yan, Chuan; Brunson, Dalton C.; Tang, Qin; Do, Daniel; Iftimia, Nicolae; Moore, John C.; Hayes, Madeline; Welker, Alessandra M.; Garcia, Elaine G.; Dubash, Taronish D.; Hong, Xin; Drapkin, Benjamin J.; Myers, David T.; Phat, Sarah; Volorio, Angela; Marvin, Dieuwke L.; Ligorio, Matteo; Dershowitz, Lyle; McCarthy, Karin M.; Karabacak, Murat; Fletcher, Jonathan A.; Sgroi, Dennis; Iafrate, John; Maheswaran, Shyamala; Dyson, Nick; Haber, Daniel A.; Rawls, John F.; Langenau, David M.

doi:10.1016/j.cell.2019.04.004

Cited by 220 publications

(274 citation statements)

References 65 publications

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“…The obtained results suggest the combination of olaparib and temozolomide as a potential treatment combination for RMS. The results further show that this drug combination leads to G2-cell-cycle arrest, already observed at 2 days post-treatment, suggesting that G2 arrest precedes apoptosis [103]. However, this study did not yet generate zPDXs directly from patient cells (cells were first expanded in vitro or derived from mPDXs), nor did it demonstrate a correlation with the patient clinical outcome, but new exciting studies are probably coming soon.…”

Section: Adult Zebrafish Xenograftsmentioning

confidence: 74%

“…Several types of zebrafish xenografts can be generated: some where human tumor cells are implanted in very early embryos, like blastula embryos [102], others in larval stages (the most commonly used), and others in adult immune compromised zebrafish strains [103]. Similar to mPDXs, cells can be implanted in different sites, including the perivitelline space (PVS), yolk sac, duct of Cuvier, eye, brain ventricles or pericardial cavity [100].…”

Section: Zebrafish Xenograftsmentioning

confidence: 99%

“…Recently, another major breakthrough was achieved in the field, with the possibility to efficiently engraft human patient-derived tumor cells into adult immunodeficient zebrafish [103]. To this end, the authors generated optically clear zebrafish mutants for protein kinase DNA-activated catalytic polypeptide (prkdc) and interleukin 2 receptor gamma (il2rg), that lack T, B, and NK cells.…”

Section: Adult Zebrafish Xenograftsmentioning

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: Adult Zebrafish Xenograftsmentioning

confidence: 74%

Section: Zebrafish Xenograftsmentioning

confidence: 99%

Section: Adult Zebrafish Xenograftsmentioning

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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“…XenoSWATH presents a paradigm shift in the ability to distinguish and comprehensively map proteomic alterations in both the human and mouse compartments and provides a new approach to investigating tumour cell-microenvironmental interactions in cancer initiation, progression and therapy response. With the recent development of human tumour xenograft models in immunodeficient zebrafish [40], we anticipate that XenoSWATH can be readily extended to the study of host and tumour cell responses in these models by similarly utilising the zebrafish reference spectral library available in SWATHAtlas [17].…”

Section: Discussionmentioning

confidence: 99%

A mouse SWATH-MS reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts

Krásný

Bland

Burns

et al. 2020

Preprint

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2 SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in 3 multiple model organisms including the mouse. Here we present a comprehensive mouse 4 reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 5 proteins (62.2% of the mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to 6 develop an analytical pipeline for species-specific deconvolution of proteomic alterations in 7 human tumour xenografts (XenoSWATH). This method overcomes the challenge of high 8 sequence similarity between mouse and human proteins, facilitating the study of host 9 microenvironment-tumour interactions from 'bulk tumour' measurements. We apply the 10 XenoSWATH pipeline to characterise an intraductal xenograft model of breast ductal 11 carcinoma in-situ and uncover complex regulation of cell migration pathways that are not 12 restricted to tumour cells but also operate in the mouse stroma upon progression to invasive 13 disease. MouseRefSWATH and XenoSWATH opens new opportunities for in-depth and 14 reproducible proteomic assessment to address wide-ranging biological questions involving 15 this important model organism. 16 17 18 19Key to the success of SWATH-MS is the use of retention-time calibrated spectral libraries to 20 identify and quantify peptides from the complex fragment ion mass spectra encoded within 21 digital proteome maps [13]. While most published SWATH-MS studies have utilised study-22

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“…Adult zebrafish are now used extensively as models throughout the biomedical research sector including areas as varied as infectious disease susceptibility and immune system function, ageing, toxicology, oncology and behaviour (Aleström, Holter, & Nourizadeh‐Lillabadi, 2006; Lin, Chiang, & Tsai, 2016; Naert & Vleminckx, 2018; Santoriello & Zon, 2012). The zebrafish is being used as a model for cancer (Liu & Leach, 2011; Yen, White, & Stemple, 2014), with studies involving transplantation of human tumours into immune‐compromised zebrafish (Taylor & Zon, 2009; Veinotte, Dellaire, & Berman, 2014; Yan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Review of diseases and health management in zebrafish Danio rerio (Hamilton 1822) in research facilities

Kent

Sanders

Spagnoli

et al. 2020

Journal of Fish Diseases

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The use of zebrafish (Danio rerio) in biomedical research has expanded at a tremendous rate over the last two decades. Along with increases in laboratories using this model, we are discovering new and important diseases. We review here the important pathogens and diseases based on some 20 years of research and findings from our diagnostic service at the NIH-funded Zebrafish International Resource Center. Descriptions of the present status of biosecurity programmes and diagnostic and treatment approaches are included. The most common and important diseases and pathogens are two parasites, Pseudoloma neurophilia and Pseudocapillaria tomentosa, and mycobacteriosis caused by Mycobacterium chelonae, M. marinum and M. haemophilum. Less common but deadly diseases are caused by Edwardsiella ictaluri and infectious spleen and kidney necrosis virus (ISKNV). Hepatic megalocytosis and eggassociated inflammation and fibroplasia are common, apparently non-infectious, in zebrafish laboratories. Water quality diseases include supersaturation and nephrocalcinosis. Common neoplasms are spindle cell sarcomas, ultimobranchial tumours, spermatocytic seminomas and a small-cell carcinoma that is caused by a transmissible agent. Despite the clear biosecurity risk, researchers continue to use fish from pet stores, and here, we document two novel coccidia associated with significant lesions in zebrafish from one of these stores. K E Y W O R D S biosecurity, Danio rerio, diagnostics, fish diseases, treatment

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Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish

Cited by 220 publications

References 65 publications

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

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

A mouse SWATH-MS reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts

Review of diseases and health management in zebrafish Danio rerio (Hamilton 1822) in research facilities

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