Repurposing metformin, simvastatin and digoxin as a combination for targeted therapy for pancreatic ductal...

Area of Science:

• Oncology
• Drug Discovery
• Genomics

Background:

• Pancreatic adenocarcinoma (PDAC) has a very low 5-year survival rate (8%) in the US.
• Current chemotherapies offer limited survival benefits for PDAC patients.
• There is an urgent need for effective precision targeted therapies to improve outcomes.

Purpose of the Study:

• To develop a novel combination therapy for PDAC using FDA-approved drugs.
• To target key genes, pancreaticoduodenal homeobox1 (PDX1) and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5).
• To expedite the delivery of targeted treatments to patients.

Main Methods:

• Utilized a drug discovery platform to screen an FDA-approved drug library.
• Employed super-promoters to target PDX1 and BIRC5 gene expression.
• Identified and selected metformin, simvastatin, and digoxin (C3) as a potential combination therapy.

Main Results:

• The C3 combination effectively targeted PDX1 and BIRC5 in human PDAC tumors xenografted in mice.
• The novel drug combination demonstrated efficacy without observable toxicity.
• This suggests a promising new therapeutic strategy for pancreatic cancer.

Conclusions:

• Metformin, simvastatin, and digoxin (C3) represent a novel, safe, and effective targeted therapy for pancreatic adenocarcinoma.
• This combination targets PDX1 and BIRC5, offering a potential breakthrough in PDAC treatment.
• The findings support further clinical investigation of the C3 combination for improving patient survival.