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

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Liu SH,Yu J,Creeden JF,Sutton JM,Markowiak S,Sanchez R,Nemunaitis J,Kalinoski A,Zhang JT,Damoiseaux R,Erhardt P,Brunicardi FC

doi

10.1016/j.canlet.2020.08.002

subject

Has Abstract

pub_date

2020-10-28 00:00:00

pages

97-107

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(20)30413-4

journal_volume

491

pub_type

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