Journal Article

Potential applications for biguanides in oncology

Pollak, Michael

2013

Overview

Metformin is widely prescribed for the treatment of type II diabetes. Recently, it has been proposed that this compound or related biguanides may have antineoplastic activity. Biguanides may exploit specific metabolic vulnerabilities of transformed cells by acting on them directly, or may act by indirect mechanisms that involve alterations of the host environment. Preclinical data suggest that drug exposure levels are a key determinant of proposed direct actions. With respect to indirect mechanisms, it will be important to determine whether recently demonstrated metformin-induced changes in levels of candidate systemic mediators such as insulin or inflammatory cytokines are of sufficient magnitude to achieve therapeutic benefit. Results of the first generation of clinical trials now in progress are eagerly anticipated. Ongoing investigations may justify a second generation of trials that explore pharmacokinetic optimization, rational drug combinations, synthetic lethality strategies, novel biguanides, and the use of predictive biomarkers.

• Publisher: American Society for Clinical Investigation
• Subject: Antimetabolites, Antineoplastic - pharmacokinetics / Antimetabolites, Antineoplastic - pharmacology / Antimetabolites, Antineoplastic - therapeutic use / Antimitotic agents / Antineoplastic agents / Biguanides / Biguanides - pharmacokinetics / Biguanides - pharmacology / Biguanides - therapeutic use / Biomedical research / Cancer therapies / Clinical trials / Clinical Trials as Topic / Diabetes / Dosage and administration / Drug discovery / Drug dosages / Drug Resistance, Neoplasm / Drug Synergism / Energy Metabolism / Humans / Hypotheses / Insulin / Metabolism / Metformin / Molecular Targeted Therapy / Mortality / Neoplasms - drug therapy / Neoplasms - metabolism / Oncology / Phosphorylation / Review Series / Rodents / Studies