Repurposing metformin, simvastatin and digoxin as a combination for targeted therapy for pancreatic ductal adenocarcinoma.
Animals
Carcinoma, Pancreatic Ductal
/ drug therapy
Cell Line, Tumor
Digoxin
/ administration & dosage
Drug Combinations
Drug Repositioning
Drug Synergism
High-Throughput Screening Assays
Homeodomain Proteins
/ antagonists & inhibitors
Humans
Male
Metformin
/ administration & dosage
Mice
Molecular Targeted Therapy
Pancreatic Neoplasms
/ drug therapy
Simvastatin
/ administration & dosage
Survivin
/ antagonists & inhibitors
Trans-Activators
/ antagonists & inhibitors
BIRC5
FDA Approved drug libraries
High throughput screening
PDX1
Super promoter
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
28 10 2020
28 10 2020
Historique:
received:
30
04
2020
revised:
23
07
2020
accepted:
01
08
2020
pubmed:
24
8
2020
medline:
23
2
2021
entrez:
24
8
2020
Statut:
ppublish
Résumé
Patients with pancreatic adenocarcinoma (PDAC) have a 5-year survival rate of 8%, the lowest of any cancer in the United States. Traditional chemotherapeutic regimens, such as gemcitabine- and fluorouracil-based regimens, often only prolong survival by months. Effective precision targeted therapy is therefore urgently needed to substantially improve survival. In an effort to expedite approval and delivery of targeted therapy to patients, we utilized a platform to develop a novel combination of FDA approved drugs that would target pancreaticoduodenal homeobox1 (PDX1) and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) utilizing super-promoters of the target genes to interrogate an FDA approved drug library. We identified and selected metformin, simvastatin and digoxin (C3) as a novel combination of FDA approved drugs, which were shown to effectively target PDX1 and BIRC5 in human PDAC tumors in mice with no toxicity.
Identifiants
pubmed: 32829010
pii: S0304-3835(20)30413-4
doi: 10.1016/j.canlet.2020.08.002
pmc: PMC8766172
mid: NIHMS1762122
pii:
doi:
Substances chimiques
Drug Combinations
0
Homeodomain Proteins
0
Survivin
0
Trans-Activators
0
pancreatic and duodenal homeobox 1 protein
0
Digoxin
73K4184T59
Metformin
9100L32L2N
Simvastatin
AGG2FN16EV
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
97-107Subventions
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
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