Use of zebrafish embryos as avatar of patients with pancreatic cancer: A new xenotransplantation model towards personalized medicine

Franco, Gregorio Di; Usai, Alice; Funel, Niccola; Palmeri, Matteo; Montesanti, Ida Elena Rosamaria; Bianchini, Matteo; Gianardi, Desirée; Furbetta, Niccolò; Guadagni, Simone; Vasile, Enrico; Falcone, Alfredo; Pollina, Luca Emanuele; Raffa, Vittoria; Morelli, Luca

doi:10.3748/wjg.v26.i21.2792

Cited by 25 publications

(28 citation statements)

References 49 publications

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“…In our preliminary experience recently published, we reported very encouraging preliminary results [10]. First, we observed the possibility of directly xenotransplanting tissue taken from PDAC in zebrafish embryos, obtaining in all cases of the control group an increase of the relative tumor area (2 dpi/1 dpi).…”

Section: Discussionmentioning

confidence: 66%

“…The strategy that we developed in our zPDX model has the distinct advantage of preserving the tumor-associated stroma and the microenvironmental factors, maintaining the original tumor architecture and the histological characteristics, as we reported in our previous article, in which, at histological examination, we observed the presence of both epithelial cells and stromal cells, with a percentage of epithelial cells (mean PDAC counterpart) out of the total surface area similar to that of the pancreatic tumor tissue [10].…”

Section: Discussionmentioning

confidence: 85%

“…Nowadays, the promising PDAC preclinical models are the patient-derived organoids (PDO), such as an in vitro system wherein progenitor cells are cultured in 3 dimensions (3D) with the possibility of reconstituting niches more similar to PDAC [8,9] or in vivo patient-derived xenografts (PDXs) with zebrafish (zPDX, Danio rerio) or mouse (mPDX, Mus musculus) as recipients [10,11]. PDXs are developed by implanting patient tumor tissue or primary cells into the animal models, recapitulating and maintaining the main features of the original tumor, and they can be used in drug efficacy studies [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, in this study, we present the outcome of the first zebrafish larval co-clinical trial [22] conducted by our research group [10,23], adding a comparison of the tests performed on zPDXs with clinical data on responses to adjuvant chemotherapy, with the aim of addressing the question: "Will a specific patient benefit from a chemotherapy regimen?". Compared to the well-consolidated procedure of isolated cancer-cell xenografts, we adopted an approach consisting of the xenotransplantation of pieces of the patient tumor tissue into zebrafish embryos, which have not yet developed an adaptive immune response (XenoZ, NCT03668418).…”

Section: Introductionmentioning

confidence: 99%

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Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients

Usai

Franco

Piccardi

et al. 2021

Cancers

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It is increasingly evident the necessity of new predictive tools for the treatment of pancreatic ductal adenocarcinoma in a personalized manner. We present a co-clinical trial testing the predictiveness of zPDX (zebrafish patient-derived xenograft) for assessing if patients could benefit from a therapeutic strategy (ClinicalTrials.gov: XenoZ, NCT03668418). zPDX are generated xenografting tumor tissues in zebrafish embryos. zPDX were exposed to chemotherapy regimens commonly used. We considered a zPDX a responder (R) when a decrease ≥50% in the relative tumor area was reported; otherwise, we considered them a non-responder (NR). Patients were classified as Responder if their own zPDX was classified as an R for the chemotherapy scheme she/he received an adjuvant treatment; otherwise, we considered them a Non-Responder. We compared the cancer recurrence rate at 1 year after surgery and the disease-free survival (DFS) of patients of both groups. We reported a statistically significant higher recurrence rate in the Non-Responder group: 66.7% vs. 14.3% (p = 0.036), anticipating relapse/no relapse within 1 year after surgery in 12/16 patients. The mean DFS was longer in the R-group than the NR-group, even if not statistically significant: 19.2 months vs. 12.7 months, (p = 0.123). The proposed strategy could potentially improve preclinical evaluation of treatment modalities and may enable prospective therapeutic selection in everyday clinical practice.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients

Usai

Franco

Piccardi

et al. 2021

Cancers

Self Cite

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“…In regard to xenotransplantation, ZF models nowadays represent a well-known option for implementing strategies of personalized medicine, together with other models of patient-derived xenografts or patient-derived organoids [ 109 , 110 ]. The efficiency and the growth of human cancer cells in ZF was firstly reported in 2005 [ 111 ] when authors evidenced many similarities in the behavior of tumors developed in mammalian models, putting the basis for further employment of ZF into this field.…”

Section: Zebrafish (Zf) As An Animal Model To Mimic Human Cancermentioning

confidence: 99%

Nanoparticles-Based Oligonucleotides Delivery in Cancer: Role of Zebrafish as Animal Model

Toffoli

Macor

et al. 2021

Pharmaceutics

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Oligonucleotide (ON) therapeutics are molecular target agents composed of chemically synthesized DNA or RNA molecules capable of inhibiting gene expression or protein function. How ON therapeutics can efficiently reach the inside of target cells remains a problem still to be solved in the majority of potential clinical applications. The chemical structure of ON compounds could affect their capability to pass through the plasma membrane. Other key factors are nuclease degradation in the extracellular space, renal clearance, reticulo-endothelial system, and at the target cell level, the endolysosomal system and the possible export via exocytosis. Several delivery platforms have been proposed to overcome these limits including the use of lipidic, polymeric, and inorganic nanoparticles, or hybrids between them. The possibility of evaluating the efficacy of the proposed therapeutic strategies in useful in vivo models is still a pivotal need, and the employment of zebrafish (ZF) models could expand the range of possibilities. In this review, we briefly describe the main ON therapeutics proposed for anticancer treatment, and the different strategies employed for their delivery to cancer cells. The principal features of ZF models and the pros and cons of their employment in the development of ON-based therapeutic strategies are also discussed.

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Progress in building clinically relevant patient‐derived tumor xenograft models for cancer research

Wang,

Li,

Lin

et al. 2023

Anim Models and Exp Med

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Patient‐derived tumor xenograft (PDX) models, a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice, have emerged as a pivotal approach in translational research, particularly in advancing precision medicine. As the first stage of PDX development, the patient‐derived orthotopic xenograft (PDOX) models implant tumor tissue in mice in the corresponding anatomical locations of the patient. The PDOX models have several advantages, including high fidelity to the original tumor, heightened drug sensitivity, and an elevated rate of successful transplantation. However, the PDOX models present significant challenges, requiring advanced surgical techniques and resource‐intensive imaging technologies, which limit its application. And then, the humanized mouse models, as well as the zebrafish models, were developed. Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay. The humanized mouse models are a hot topic in PDX model research. Regarding zebrafish patient‐derived tumor xenografts (zPDX) and patient‐derived organoids (PDO) as promising models for studying cancer and drug discovery, zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time. PDO models provide a cost‐effective approach for drug testing that replicates the in vivo environment and preserves important tumor‐related information for patients. The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.

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Use of zebrafish embryos as avatar of patients with pancreatic cancer: A new xenotransplantation model towards personalized medicine

Cited by 25 publications

References 49 publications

Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients

Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients

Nanoparticles-Based Oligonucleotides Delivery in Cancer: Role of Zebrafish as Animal Model

Progress in building clinically relevant patient‐derived tumor xenograft models for cancer research

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