Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening.
Albumins
/ therapeutic use
Animals
Antineoplastic Agents
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Deoxycytidine
/ analogs & derivatives
Drug Therapy, Combination
Fluorouracil
/ therapeutic use
Irinotecan
/ therapeutic use
Leucovorin
/ therapeutic use
Oxaliplatin
/ therapeutic use
Paclitaxel
/ therapeutic use
Pancreatic Neoplasms
/ drug therapy
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
/ methods
Zebrafish
Gemcitabine
ampullary tumors
chemotherapy
pancreatic cancer
personalized medicine
zAvatars
zebrafish xenografts
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
13 08 2021
13 08 2021
Historique:
received:
22
07
2021
revised:
06
08
2021
accepted:
10
08
2021
entrez:
27
8
2021
pubmed:
28
8
2021
medline:
18
11
2021
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Identifiants
pubmed: 34440847
pii: cells10082077
doi: 10.3390/cells10082077
pmc: PMC8393525
pii:
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
Antineoplastic Agents
0
folfirinox
0
Oxaliplatin
04ZR38536J
Deoxycytidine
0W860991D6
Irinotecan
7673326042
Paclitaxel
P88XT4IS4D
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Gemcitabine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fundação Champalimaud
ID : #168
Organisme : Fundação para a Ciência e a Tecnologia
ID : FCT-PTDC/MEC-ONC/31627/ 2017
Organisme : Fundação para a Ciência e a Tecnologia
ID : LISBOA-01-0145-FEDER-022170, co-financed by FCT/Lisboa2020
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