Journal ArticleDOI
Repositioning metformin for cancer prevention and treatment.
TLDR
Improved understanding of these issues will increase the chances for successful application of metformin as an inexpensive, well-tolerated, and effective anticancer agent.Abstract:
Metformin is the most commonly prescribed drug for type 2 diabetes (T2DM). Retrospective studies show that metformin is associated with decreased cancer risk. This historical correlation has driven vigorous research campaigns to determine the anticancer mechanisms of metformin. Consolidating the preclinical data is a challenge because unanswered questions remain concerning relevant mechanisms, bioavailability, and genetic factors that confer metformin sensitivity. Perhaps the most important unanswered question is whether metformin has activity against cancer in non-diabetics. In this review we highlight the proposed mechanisms of metformin action in cancer and discuss ongoing clinical trials with metformin in cancer. Improved understanding of these issues will increase the chances for successful application of metformin as an inexpensive, well-tolerated, and effective anticancer agent.read more
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AMPK: guardian of metabolism and mitochondrial homeostasis.
Sébastien Herzig,Reuben J. Shaw +1 more
TL;DR: How AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology is discussed.
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Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies.
TL;DR: The aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy are discussed.
Journal ArticleDOI
Gasotransmitters in cancer: from pathophysiology to experimental therapy
TL;DR: The role of each gasotransmitter in cancer and the effects of pharmacological agents — some of which are in early-stage clinical studies — that modulate the levels of eachGasotransmitters are discussed.
Journal ArticleDOI
A survey of current trends in computational drug repositioning
TL;DR: This review of recent advancements in the critical areas of computational drug repositioning from multiple aspects shows potential opportunities and use-cases, including a few target areas such as cancers.
Journal ArticleDOI
Modulating the therapeutic response of tumours to dietary serine and glycine starvation
Oliver D. K. Maddocks,Dimitris Athineos,Eric C. Cheung,Pearl Lee,Tong Zhang,Niels J. F. van den Broek,Gillian M. Mackay,Christiaan F. Labuschagne,Flore Kruiswijk,Julianna Blagih,David F. Vincent,Kirsteen J. Campbell,Fatih Ceteci,Owen J. Sansom,Karen Blyth,Karen H. Vousden +15 more
TL;DR: The authors showed that restricting dietary serine and glycine can reduce tumour growth in xenograft and allograft models, and this observation translates into more clinically relevant autochthonous tumours in genetically engineered mouse models of intestinal cancer or lymphoma.
References
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Journal ArticleDOI
Hallmarks of cancer: the next generation.
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
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Role of AMP-activated protein kinase in mechanism of metformin action
Gaochao Zhou,Robert W. Myers,Ying Li,Yuli Chen,Xiaolan Shen,Judy Fenyk-Melody,Margaret Wu,John Ventre,Thomas W. Doebber,Nobuharu Fujii,Nicolas Musi,Michael F. Hirshman,Laurie J. Goodyear,David E. Moller +13 more
TL;DR: It is reported that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed.
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Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis
TL;DR: A detailed understanding of epidemiologic factors and molecular mechanisms associated with HCC ultimately could improve current concepts for screening and treatment of this disease.
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TSC2 mediates cellular energy response to control cell growth and survival.
TL;DR: It is described that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis.
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AMPK: a nutrient and energy sensor that maintains energy homeostasis
TL;DR: AMP-activated protein kinase conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability.