Zebrafish Cancer Avatars: A Translational Platform for Analyzing Tumor Heterogeneity and Predicting Patient Outcomes

Al-Hamaly, Majd A.; Turner, Logan T.; Rivera-Martinez, Angelica; Rodriguez, Analiz; Blackburn, Jessica S.

doi:10.3390/ijms24032288

Cited by 13 publications

(9 citation statements)

References 143 publications

(185 reference statements)

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“…Many studies have indicated that ZTX models can be used to predict the response of solid tumours to various therapies 35 . For example, a gastric cancer study 19 reported the successful injection of cells from 28 patients (from a total of 46).…”

Section: Discussionmentioning

confidence: 99%

Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancer

Lindahl,

Fjellander,

Selvaraj

et al. 2024

npj Precis. Onc.

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Epithelial ovarian cancer (EOC) is the gynaecological malignancy with highest mortality. Although adjuvant treatment with carboplatin and paclitaxel leads to an objective response in ~80% of these patients, a majority will relapse within two years. Better methods for assessing long-term treatment outcomes are needed. To address this, we established safe and efficacious doses of carboplatin and paclitaxel using IGROV-1 zebrafish-CDX models. Then fluorescently-labelled cell suspensions from 83 tumour biopsies collected at exploratory laparotomy of women with suspected EOC were generated and 37 (45%) were successfully implanted in zebrafish larvae. Among these 19 of 27 pathology-confirmed EOC samples (70%) engrafted. These zebrafish patient-derived tumour xenograft (ZTX) models were treated with carboplatin or paclitaxel and tumour growth/regression and metastatic dissemination were recorded. In a subgroup of nine patients, four ZTX models regressed during carboplatin treatment. All four corresponding patients had >24 months PFS. Furthermore, both ZTX models established from two patients having <24 months PFS failed to regress during carboplatin treatment. Seven of eight models seeding <6 metastatic cells were established from patients having >24 months PFS. In eleven of fourteen patients, FIGO stage I + II or III tumours gave rise to ZTX models seeding <4 or >4 metastatic cells, respectively. In conclusion, ZTX models predicted patients having >24 or <24 months PFS, based on response/no response to carboplatin. Furthermore, high metastatic dissemination in ZTX models correlated to shorter PFS and more advanced disease at diagnosis. These preliminary results suggest that ZTX models could become a useful prognostic tool in EOC treatment planning.

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Section: Discussionmentioning

confidence: 99%

Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancer

Lindahl,

Fjellander,

Selvaraj

et al. 2024

npj Precis. Onc.

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“…In fact, zebrafish is emerging as a timeand cost-effective cancer avatar model to assess tumor phenotype and drug responses. For instance, zebrafish patient-derived xenografts (zPDX) may be suitable for providing precision cancer-medicine pipelines [82].…”

Section: Neuro-phenotypic Complexity In Rasopathies With Insights Fro...mentioning

confidence: 99%

“…zebrafish patient-derived xenografts (zPDX) may be suitable for providing precision cancer-medicine pipelines [82].…”

Section: Neuro-phenotypic Complexity In Rasopathies With Insights Fro...mentioning

confidence: 99%

Non-Mammalian Models for Understanding Neurological Defects in RASopathies

Rodríguez-Martín,

Báez-Flores,

Ribes

et al. 2024

Biomedicines

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RASopathies, a group of neurodevelopmental congenital disorders stemming from mutations in the RAS/MAPK pathway, present a unique opportunity to delve into the intricacies of complex neurological disorders. Afflicting approximately one in a thousand newborns, RASopathies manifest as abnormalities across multiple organ systems, with a pronounced impact on the central and peripheral nervous system. In the pursuit of understanding RASopathies’ neurobiology and establishing phenotype–genotype relationships, in vivo non-mammalian models have emerged as indispensable tools. Species such as Danio rerio, Drosophila melanogaster, Caenorhabditis elegans, Xenopus species and Gallus gallus embryos have proven to be invaluable in shedding light on the intricate pathways implicated in RASopathies. Despite some inherent weaknesses, these genetic models offer distinct advantages over traditional rodent models, providing a holistic perspective on complex genetics, multi-organ involvement, and the interplay among various pathway components, offering insights into the pathophysiological aspects of mutations-driven symptoms. This review underscores the value of investigating the genetic basis of RASopathies for unraveling the underlying mechanisms contributing to broader neurological complexities. It also emphasizes the pivotal role of non-mammalian models in serving as a crucial preliminary step for the development of innovative therapeutic strategies.

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“…Future cancer studies can further study the role of angiogenesis [ 122 ] and better mimic the human tumor microenvironment [ 129 ], including creating humanized models as achieved in mice [ 142 ]. Finally, so-called cancer ‘avatars’ have application in patient-specific ‘precision’ cancer therapy pipelines, with the potential to directly predict patient outcomes and thus influence individual patient care [ 143 , 144 ].…”

Section: Limitations and Future Prospectsmentioning

confidence: 99%

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

Basheer

Sertori

Liongue

et al. 2023

IJMS

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Primary immunodeficiency (PID) disorders, also commonly referred to as inborn errors of immunity, are a heterogenous group of human genetic diseases characterized by defects in immune cell development and/or function. Since these disorders are generally uncommon and occur on a variable background profile of potential genetic and environmental modifiers, animal models are critical to provide mechanistic insights as well as to create platforms to underpin therapeutic development. This review aims to review the relevance of zebrafish as an alternative genetic model for PIDs. It provides an overview of the conservation of the zebrafish immune system and details specific examples of zebrafish models for a multitude of specific human PIDs across a range of distinct categories, including severe combined immunodeficiency (SCID), combined immunodeficiency (CID), multi-system immunodeficiency, autoinflammatory disorders, neutropenia and defects in leucocyte mobility and respiratory burst. It also describes some of the diverse applications of these models, particularly in the fields of microbiology, immunology, regenerative biology and oncology.

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Zebrafish Cancer Avatars: A Translational Platform for Analyzing Tumor Heterogeneity and Predicting Patient Outcomes

Cited by 13 publications

References 143 publications

Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancer

Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancer

Non-Mammalian Models for Understanding Neurological Defects in RASopathies

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

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