Faculty Collaboration Database

Patient- and Cell Type-Specific Heterogeneity of Metformin Response. Basic Clin Pharmacol Toxicol 2018 Feb;122(2):214-222

Date

09/02/2017

Pubmed ID

28862803

DOI

10.1111/bcpt.12898

Scopus ID

2-s2.0-85030121920 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Most FDA-approved drugs are not equally effective in all patients, suggesting that identification of biomarkers to predict responders to a chemoprevention agent will be needed to stratify patients and achieve maximum benefit. The goal of this study was to investigate both patient-specific and cell context-specific heterogeneity of metformin response, using fibroblast cell lines and induced pluripotent stem cells differentiated into lung epithelial lineages. We performed cell survival analysis, transcriptome and whole exome sequencing analysis on both patient-derived cell lines and cancer cell lines to assess differential metformin response and identify response genes. We found differences in response to metformin treatment across a variety of cell lines and cellular contexts, suggesting that heterogeneity may be patient- and cell type-specific. Gene expression profiling and analysis of metformin-sensitive and metformin-resistant cells identified differentially expressed genes that may be able to stratify patients into metformin responders and non-responders. Sequencing analysis found genomic alterations that correlated with metformin response. These results suggest that the identification of genomic biomarkers for patients who may respond to metformin treatment can provide an opportunity for individualizing metformin chemoprevention in the clinical setting.

Author List

Asiedu MK, Barron M, Aubry MC, Wigle DA

Author

Matthew R. Barron Research Scientist I in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Cell Differentiation
Cell Line, Tumor
Cell Lineage
Cell Survival
Dose-Response Relationship, Drug
Drug Resistance
Epithelial Cells
Fibroblasts
Gene Expression Profiling
Genetic Heterogeneity
Humans
Induced Pluripotent Stem Cells
Metformin
Neoplasms
Pharmacogenetics
Phenotype
Precision Medicine
Transcriptome