Investigating Metformin for Cancer Prevention and Treatment: The End of the Beginning

被引:410
作者
Pollak, Michael N. [1 ]
机构
[1] McGill Univ, Jewish Gen Hosp, Dept Oncol, Segal Canc Ctr,Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada
基金
加拿大健康研究院;
关键词
ACTIVATED PROTEIN-KINASE; STAGE BREAST-CANCER; PLASMA C-PEPTIDE; DIABETIC-PATIENTS; PROSTATE-CANCER; INSULIN SENSITIVITY; COLORECTAL-CANCER; RANDOMIZED-TRIAL; GROWTH; AMPK;
D O I
10.1158/2159-8290.CD-12-0263
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Laboratory research and pharmacoepidemiology are providing converging evidence that the widely used antidiabetic drug metformin has antineoplastic activity, but there are caveats. Although population studies suggest that metformin exposure is associated with reduced cancer risk and/or improved prognosis, these data are mostly retrospective and nonrandomized. Laboratory models show antineoplastic activity, but metformin concentrations used in many experiments exceed those achieved with conventional doses used for diabetes treatment. Ongoing translational research should be useful in guiding design of clinical trials, not only to evaluate metformin at conventional antidiabetic doses, where reduction of elevated insulin levels may contribute to antineoplastic activity for certain subsets of patients, but also to explore more aggressive dosing of biguanides, which may lead to reprogramming of energy metabolism in a manner that could provide important opportunities for synthetic lethality through rational drug combinations or in the context of genetic lesions associated with hypersensitivity to energetic stress. Significance: There are tantalizing clues that justify the investigation of antineoplastic activities of biguanides. The complexity of their biologic effects requires further translational research to guide clinical trial design. Cancer Discov; 2(9); 778-90. (C) 2012 AACR.
引用
收藏
页码:778 / 790
页数:13
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