PUBLICATION

Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening

Authors
Tavares Barroso, M., Costa, B., Rebelo de Almeida, C., Castillo Martin, M., Couto, N., Carvalho, T., Fior, R.
ID
ZDB-PUB-210828-26
Date
2021
Source
Cells   10(8): (Journal)
Registered Authors
Fior, Rita
Keywords
ampullary tumors, chemotherapy, pancreatic cancer, personalized medicine, zAvatars, zebrafish xenografts
MeSH Terms
  • Albumins/therapeutic use
  • Animals
  • Antineoplastic Agents/therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
  • Deoxycytidine/analogs & derivatives
  • Deoxycytidine/therapeutic use
  • Drug Therapy, Combination
  • Fluorouracil/therapeutic use
  • Irinotecan/therapeutic use
  • Leucovorin/therapeutic use
  • Oxaliplatin/therapeutic use
  • Paclitaxel/therapeutic use
  • Pancreatic Neoplasms/drug therapy*
  • Pancreatic Neoplasms/pathology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays/methods*
  • Zebrafish
PubMed
34440847 Full text @ Cells
Abstract
Cancers of the pancreas and biliary tree remain one of the most aggressive oncological malignancies, with most patients relying on systemic chemotherapy. However, effective biomarkers to predict the best therapy option for each patient are still lacking. In this context, an assay able to evaluate individual responses prior to treatment would be of great value for clinical decisions. Here we aimed to develop such a model using zebrafish xenografts to directly challenge pancreatic cancer cells to the available chemotherapies.
Zebrafish xenografts were generated from a Panc-1 cell line to optimize the pancreatic setting. Pancreatic surgical resected samples, without in vitro expansion, were used to establish zebrafish patient-derived xenografts (zAvatars). Upon chemotherapy exposure, zAvatars were analyzed by single-cell confocal microscopy.
We show that Panc-1 zebrafish xenografts are able to reveal tumor responses to both FOLFIRINOX and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel in just 4 days. Moreover, we established pancreatic and ampullary zAvatars with patient-derived tumors representative of different histological types.
Altogether, we provide a short report showing the feasibility of generating and analyzing with single-cell resolution zAvatars from pancreatic and ampullary cancers, with potential use for future preclinical studies and personalized treatment.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping