The cell-autonomous mechanisms underlying the activity of metformin as an anticancer drug

Sacco, Francesca; Calderone, Alberto; Castagnoli, Luisa

doi:10.1038/bjc.2016.385

Cited by 24 publications

(18 citation statements)

References 50 publications

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“…In addition to its glucose lowering properties, metformin inhibits proliferation of cancer cells by suppressing the production of mitochondrial dependent metabolic intermediates needed for cell growth, and it also causes down-modulation of cell proliferation related proteins through activation of AMPK and a decrease in mTOR 6869. These actions of metformin have raised interest in the potential short and long term effects of metformin on fetal and childhood development.…”

Section: Metforminmentioning

confidence: 99%

Novel therapies for diabetes mellitus in pregnancy

Feghali

Scifres

2018

BMJ

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Diabetes is a common complication of pregnancy, and the prevalence of all types of the disease is increasing worldwide. Diabetes in pregnancy is associated with short term and long term adverse effects for mother and child. The goal of treatment of diabetes in pregnancy is to minimize maternal and fetal adverse events related to hyperglycemia. Treatment options vary by type of diabetes, from a focus on lifestyle modifications in gestational diabetes to continuous glucose monitoring and insulin pumps in pregestational diabetes. Nevertheless, given the commonality of hyperglycemia, considerable overlap exists in the treatment of different types of diabetes in pregnancy. Also, despite ongoing research on treatment of diabetes in pregnancy for decades, changes in the characteristics of the patient population have highlighted the limited effectiveness of different therapies. Specifically, despite the co-occurrence of obesity and diabetes, treatment recommendations including glycemic targets are not altered in such cases and a single optimal treatment strategy for each type of diabetes in pregnancy does not seem to exist. Rather, the approach to treating pregnant women with diabetes likely needs to be individualized to maximize the short term and long term health of mother and child. This article will review recent clinical studies to summarize established treatment strategies and introduce novel therapies for diabetes in pregnancy.

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Section: Metforminmentioning

confidence: 99%

Novel therapies for diabetes mellitus in pregnancy

Feghali

Scifres

2018

BMJ

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“…85 In addition to RCT data, our improved understanding of metformin effects, including its suppression of mitochondrial respiration, cellular growth inhibition, and gluconeogenic impact, suggest a possible impact on childhood development and support the need for further investigations regarding its use in pregnancy. 86,87 Collectively, these findings support the need for long-term offspring follow-up in studies evaluating GDM treatment and suggest a need for discretion in the use of metformin during pregnancy.…”

Section: Metforminmentioning

confidence: 65%

Drugs to Control Diabetes During Pregnancy

Feghali

Umans

Catalano

2019

Clinics in Perinatology

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Diabetes is a common complication of pregnancy associated with both short-and long-term adverse maternal and offspring effects. All types of diabetes in pregnancy are increasing in prevalence. Treatment of diabetes in pregnancy, targeting glycemic control, improves both maternal and offspring outcomes, albeit imperfectly for many women. Pharmacologic treatment recommendations differ between pre-gestational and gestational diabetes; in each case, effectiveness appears limited by co-morbid obesity due to overlapping maternal and offspring risks associated with obesity and diabetes in pregnancy. Despite changes in patient characteristics and increasing evidence of heterogeneous pathophysiology contributing to diabetes in pregnancy, current practice still presupposes a single common treatment strategy, including pharmacologic agents and glycemic targets, with little distinction by diabetes type or pathophysiologic mechanism. Furthermore, while diabetes in pregnancy is associated with long-term offspring risks, few studies have assessed long-term outcomes following exposure to different diabetes treatments in utero. Improved treatment of diabetes in pregnancy will need to consider maternal disease heterogeneity and comorbidities as well as long-term offspring outcomes. In this review, we will summarize recent clinical studies to highlight established pharmacologic treatments for diabetes in pregnancy and provide suggestions for further research.

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“…Microarray analysis of MDA-MB-468 TNBC cells cultured in media with 5 mM glucose in the presence or absence of 10 mM metformin revealed that metformin inhibited several key enzymes involved in glucose metabolism indicating that metformin may prove to be efficient in the treatment of TNBCs [186]. Several recent articles have reviewed mechanisms, such as activation of AMPK pathway, inhibition of Akt/mTOR pathway, inhibition of cell cycle progression and SP1 transcription factor regulation, whereby metformin exerts its anti-cancer effect in several different cancers [187][188][189].…”

Section: Insulin Sensitizer -Biguanides (Metformin)mentioning

confidence: 99%

Challenges and perspectives in the treatment of diabetes associated breast cancer

Samuel

Varghese

et al. 2018

Cancer Treatment Reviews

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Type 2 diabetes mellitus is one of the most common chronic disease worldwide and affects all cross-sections of the society including children, women, youth and adults. Scientific evidence has linked diabetes to higher incidence, accelerated progression and increased aggressiveness of different cancers. Among the different forms of cancer, research has reinforced a link between diabetes and the risk of breast cancer. Some studies have specifically linked diabetes to the highly aggressive, triple negative breast cancers (TNBCs) which do not respond to conventional hormonal/HER2 targeted interventions, have chances of early recurrence, metastasize, tend to be more invasive in nature and develop drug resistance. Commonly used anti-diabetic drugs, such as metformin, have recently gained importance in the treatment of breast cancer due to their proposed anti-cancer properties. Here we discuss the link between diabetes and breast cancer, the metabolic disturbances in diabetes that support the development of breast cancer, the challenges involved and future perspective and directions. We link the three main metabolic disturbances (dyslipidemia, hyperinsulinemia and hyperglycemia) that occur in diabetes to potential aberrant molecular pathways that may lead to the development of an oncogenic phenotype of the breast tissue, thereby leading to acceleration of cell growth, proliferation, migration, inflammation, angiogenesis, EMT and metastasis and inhibition of apoptosis in breast cancer cells. Furthermore, managing diabetes and treating cancer using a combination of anti-diabetic and classical anti-cancer drugs should prove to be more efficient in the treatment diabetes associated cancers.

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The cell-autonomous mechanisms underlying the activity of metformin as an anticancer drug

Cited by 24 publications

References 50 publications

Novel therapies for diabetes mellitus in pregnancy

Novel therapies for diabetes mellitus in pregnancy

Drugs to Control Diabetes During Pregnancy

Challenges and perspectives in the treatment of diabetes associated breast cancer

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