Combined treatment with glucagon-like peptide-1 receptor agonist exendin-4 and metformin attenuates breast cancer growth

Tanaka, Yuki; Iwaya, Chikayo; Kawanami, Takako; Hamaguchi, Yukihisa; Horikawa, Tsuyoshi; Shigeoka, Toru; Yanase, Toshihiko; Kawanami, Daiji; Nomiyama, Takashi

doi:10.1007/s13340-021-00560-z

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…Exendin-4 suppresses cell proliferation through the inhibition of ERK-MAPK [80]. Lastly, a combination of exendin-4 and metformin has been shown to attenuate different forms of cancer at a more noticeable rate [94,95].…”

Section: Glucagon-like Peptide-1 Receptor Agonistsmentioning

confidence: 99%

“…Semaglutide, as a GLP-1R agonist, works very similarly to GLP-1 by potentiating glucose-stimulated insulin secretion from the pancreatic β-cells while suppressing glucagon secretion by pancreatic α-cells [103]. Therefore, antidiabetic medication decreases blood sugar levels, reduces body weight through a reduction in appetite [94], and lowers glycated hemoglobin (HbA1c), all while having a low risk of causing hypoglycemia [104]. Although GLP-1R agonists exhibit protective and regulatory effects on blood glucose levels, they have been positively correlated with tumor progression in patients with diabetes [51,73].…”

Section: The Popular Glp-1r Agonist Semaglutidementioning

confidence: 99%

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The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

Ibrahim,

Arabi

et al. 2024

Cancer Metastasis Rev

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Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role of GLP-1R in type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, and facilitating insulin release. GLP-1R agonists have effectively managed obesity by reducing hunger, moderating food intake, and regulating body weight. Beyond diabetes and obesity, GLP-1R agonists exhibit a multifaceted impact on cancer progression across various malignancies. The mechanisms underlying these effects involve the modulation of signaling pathways associated with cell growth, survival, and metabolism. However, the current literature reveals a lack of in vivo studies on specific GLP-1R agonists such as semaglutide, necessitating further research to elucidate its precise mechanisms and effects, particularly in cancer. While other GLP-1R agonists have shown promising outcomes in mitigating cancer progression, the association between some GLP-1R agonists and an increased risk of cancer remains a topic requiring more profound investigation. This calls for more extensive research to unravel the intricate relationships between the GLP-1R agonist and different cancers, providing valuable insights for clinicians and researchers alike.

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Section: Glucagon-like Peptide-1 Receptor Agonistsmentioning

confidence: 99%

Section: The Popular Glp-1r Agonist Semaglutidementioning

confidence: 99%

The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

Ibrahim,

Arabi

et al. 2024

Cancer Metastasis Rev

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“…Recent studies have shown that when metformin is used in combination with other therapeutic drugs, its effectiveness will be improved. For example, glucagon-like peptide-1 receptor agonist exendin-4 (Ex-4), another anti-diabetic drug, has been proven to be effective for BC when used in combination with metformin [ 12 ] by inhibiting NF-κB [ 13 ] and modulating different RNA gene expression [ 12 ].…”

Section: Mrs Targeting Glucose Metabolismmentioning

confidence: 99%

Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer

Shum

Vadgama

et al. 2023

JPM

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In recent years, diabetes-associated breast cancer has become a significant clinical challenge. Diabetes is not only a risk factor for breast cancer but also worsens its prognosis. Patients with diabetes usually show hyperglycemia and hyperinsulinemia, which are accompanied by different glucose, protein, and lipid metabolism disorders. Metabolic abnormalities observed in diabetes can induce the occurrence and development of breast cancer. The changes in substrate availability and hormone environment not only create a favorable metabolic environment for tumorigenesis but also induce metabolic reprogramming events required for breast cancer cell transformation. Metabolic reprogramming is the basis for the development, swift proliferation, and survival of cancer cells. Metabolism must also be reprogrammed to support the energy requirements of the biosynthetic processes in cancer cells. In addition, metabolic reprogramming is essential to enable cancer cells to overcome apoptosis signals and promote invasion and metastasis. This review aims to describe the major metabolic changes in diabetes and outline how cancer cells can use cellular metabolic changes to drive abnormal growth and proliferation. We will specifically examine the mechanism of metabolic reprogramming by which diabetes may promote the development of breast cancer, focusing on the role of glucose metabolism, amino acid metabolism, and lipid metabolism in this process and potential therapeutic targets. Although diabetes-associated breast cancer has always been a common health problem, research focused on finding treatments suitable for the specific needs of patients with concurrent conditions is still limited. Most studies are still currently in the pre-clinical stage and mainly focus on reprogramming the glucose metabolism. More research targeting the amino acid and lipid metabolism is needed.

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Redirection to the Drug Discovery: Antidiabetic Drugs Repurposing in Cancer

Bule,

Kolipaka,

Ranvare

et al. 2024

Drug Repurposing

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Combined treatment with glucagon-like peptide-1 receptor agonist exendin-4 and metformin attenuates breast cancer growth

Cited by 4 publications

References 32 publications

The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer

Redirection to the Drug Discovery: Antidiabetic Drugs Repurposing in Cancer

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