Metformin in cancer: translational challenges

被引：273

作者：

Dowling, Ryan J. O. ^{[2
,3
]}

Niraula, Saroj ^{[3
]}

Stambolic, Vuk ^{[2
,3
]}

Goodwin, Pamela J. ^{[1
]}

机构：

[1] Univ Toronto, Div Clin Epidemiol, Dept Med, Samuel Lunenfeld Res Inst,Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada

[2] Univ Hlth Network, Div Signalling Biol, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada

[3] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada

来源：

JOURNAL OF MOLECULAR ENDOCRINOLOGY | 2012年 / 48卷 / 03期

基金：

加拿大健康研究院;

关键词：

ACTIVATED PROTEIN-KINASE; STAGE BREAST-CANCER; TYPE-2; DIABETIC-PATIENTS; CELL-CYCLE ARREST; PROSTATE-CANCER; PANCREATIC-CANCER; HEPATOCELLULAR-CARCINOMA; METABOLIC CHECKPOINT; PROSPECTIVE COHORT; INSULIN-RECEPTOR;

D O I：

10.1530/JME-12-0007

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The anti-diabetic drug metformin is rapidly emerging as a potential anti-cancer agent. Metformin, effective in treating type 2 diabetes and the insulin resistance syndromes, improves insulin resistance by reducing hepatic gluconeogenesis and by enhancing glucose uptake by skeletal muscle. Epidemiological studies have consistently associated metformin use with decreased cancer incidence and cancer-related mortality. Furthermore, numerous preclinical and clinical studies have demonstrated anti-cancer effects of metformin, leading to an explosion of interest in evaluating this agent in human cancer. The effects of metformin on circulating insulin levels indicate a potential efficacy towards cancers associated with hyperinsulinaemia; however, metformin may also directly inhibit tumour growth. In this review, we describe the mechanism of action of metformin and summarise the epidemiological, clinical and preclinical evidence supporting a role for metformin in the treatment of cancer. In addition, the challenges associated with translating preclinical results into therapeutic benefit in the clinical setting will be discussed. Journal of Molecular Endocrinology (2012) 48, R31-R43

引用

页码：R31 / R43

页数：13

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