Metformin in pancreatic cancer treatment: from clinical trials through basic research to biomarker quantification
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Three major chemotherapy strategies have emerged in the treatment of PDAC in the recent past: multiple drug combination, stroma depletion, and use of nanodrug therapy. Anti-diabetic metformin was shown to improve the outcome of a number of cancer types the first seminal report on an observational study published in 2005 and the first hospital-based case–control study on pancreatic cancer in 2009.
In this review paper, we confront the findings of a selected number of epidemiological studies and clinical trials on the use of metformin in pancreatic cancer treatment with basic knowledge and research. We particularly emphasize on the point that contradictory clinical results likely originate from heterogeneous study design due to a trial and error approach rather than an evidence-based and scientific approach. A non-rigorous selection of patients suffering from PDAC and often a poor understanding of the biological mechanism of metformin coupled with lack of scientific data has led to general statements on metformin positive or negative action, another aspect which we highlight in the review.
We here present a few pathways which in our opinion are predominant for pancreatic cancer specifically: mitochondrial activity, AMPK activation, mTOR inhibition, and decreased IGF-1R and HIF-1α expression.
We stress on the need for a better stratification of patients and a more rigorous planning of clinical trials not only focusing on classical parameters but also on potential predictive biomarkers (AMPK, mTOR, HIF-1α, IGF-1R) and metformin dosage for positive outcome.
KeywordsMetformin Pancreatic cancer Cancer biology Clinical trials Biomarkers
Protein kinase B
5′ Adenosine monophosphate-activated protein kinase
Advanced pancreatic cancer
Epidermal growth factor
Extracellular signal-regulated kinase
Insulin-like growth factor
Insulin-like growth factor 1 receptor
Mammalian target of rapamycin
Mitogen-activated protein kinase
Metastatic pancreatic cancer
Nuclear factor kappa B
Phosphatase and tensin homologue
Seven in abstensia homologue
Signal transducer and activator of transcription 3
Type 2 diabetes mellitus
The authors are indebted to the Mauritius Research Council for funding drug delivery research.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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