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Repurposing Metformin, Simvastatin and Digoxin as a combination for Targeted therapy of Pancreatic Ductal Adenocarcinoma
- Source :
- Cancer Lett
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Oncology
Male
Cancer Research
Digoxin
Simvastatin
endocrine system diseases
medicine.medical_treatment
Survivin
Targeted therapy
Mice
0302 clinical medicine
Super promoter
Molecular Targeted Therapy
Cancer
PDX1
Tumor
BIRC5
Drug Synergism
Metformin
Drug Combinations
Pancreatic Ductal
5.1 Pharmaceuticals
6.1 Pharmaceuticals
030220 oncology & carcinogenesis
Adenocarcinoma
Development of treatments and therapeutic interventions
Biotechnology
medicine.drug
Carcinoma, Pancreatic Ductal
medicine.medical_specialty
Oncology and Carcinogenesis
Approved drug
Article
Cell Line
FDA Approved drug libraries
Pancreatic Cancer
03 medical and health sciences
Rare Diseases
High throughput screening
Internal medicine
Cell Line, Tumor
medicine
Animals
Humans
Oncology & Carcinogenesis
Survival rate
Homeodomain Proteins
business.industry
Carcinoma
Drug Repositioning
Evaluation of treatments and therapeutic interventions
medicine.disease
Gemcitabine
High-Throughput Screening Assays
Pancreatic Neoplasms
Orphan Drug
Good Health and Well Being
030104 developmental biology
Trans-Activators
Digestive Diseases
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cancer Lett
- Accession number :
- edsair.doi.dedup.....43ce0bbc70998c0f54428dce7848204e