Anti-Diabetic Therapies and Cancer: From Bench to Bedside

Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention for its potential anti-cancer effects, primarily through modulation of the AM...

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Main Authors: Dimitris Kounatidis, Natalia G. Vallianou, Irene Karampela, Eleni Rebelos, Marina Kouveletsou, Vasileios Dalopoulos, Petros Koufopoulos, Evanthia Diakoumopoulou, Nikolaos Tentolouris, Maria Dalamaga
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Language:English
Published: MDPI AG 2024-11-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/14/11/1479
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author Dimitris Kounatidis
Natalia G. Vallianou
Irene Karampela
Eleni Rebelos
Marina Kouveletsou
Vasileios Dalopoulos
Petros Koufopoulos
Evanthia Diakoumopoulou
Nikolaos Tentolouris
Maria Dalamaga
author_facet Dimitris Kounatidis
Natalia G. Vallianou
Irene Karampela
Eleni Rebelos
Marina Kouveletsou
Vasileios Dalopoulos
Petros Koufopoulos
Evanthia Diakoumopoulou
Nikolaos Tentolouris
Maria Dalamaga
author_sort Dimitris Kounatidis
collection DOAJ
description Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention for its potential anti-cancer effects, primarily through modulation of the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway and the induction of autophagy. Beyond metformin, other conventional anti-diabetic treatments, such as insulin, sulfonylureas (SUs), pioglitazone, and dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined for their roles in cancer biology, though findings are often inconclusive. More recently, novel medications, like glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, have revolutionized DM management by not only improving glycemic control but also delivering substantial cardiovascular and renal benefits. Given their diverse metabolic effects, including anti-obesogenic properties, these novel agents are now under meticulous investigation for their potential influence on tumorigenesis and cancer advancement. This review aims to offer a comprehensive exploration of the evolving landscape of glucose-lowering treatments and their implications in cancer biology. It critically evaluates experimental evidence surrounding the molecular mechanisms by which these medications may modulate oncogenic signaling pathways and reshape the tumor microenvironment (TME). Furthermore, it assesses translational research and clinical trials to gauge the practical relevance of these findings in real-world settings. Finally, it explores the potential of anti-diabetic medications as adjuncts in cancer treatment, particularly in enhancing the efficacy of chemotherapy, minimizing toxicity, and addressing resistance within the framework of immunotherapy.
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spelling doaj-art-2c5261fefe1248bb8c58a6e53519538a2024-11-26T17:54:29ZengMDPI AGBiomolecules2218-273X2024-11-011411147910.3390/biom14111479Anti-Diabetic Therapies and Cancer: From Bench to BedsideDimitris Kounatidis0Natalia G. Vallianou1Irene Karampela2Eleni Rebelos3Marina Kouveletsou4Vasileios Dalopoulos5Petros Koufopoulos6Evanthia Diakoumopoulou7Nikolaos Tentolouris8Maria Dalamaga9Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, GreeceFirst Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece2nd Department of Critical Care, Medical School, Attikon General University Hospital, University of Athens, 1 Rimini str., 12461 Athens, GreeceDiabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, GreeceDiabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, GreeceFirst Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, GreeceFirst Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, GreeceDiabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, GreeceDiabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, GreeceDepartment of Biological Chemistry, National and Kapodistrian University of Athens, 75 Mikras Asias str., 11527 Athens, GreeceDiabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention for its potential anti-cancer effects, primarily through modulation of the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway and the induction of autophagy. Beyond metformin, other conventional anti-diabetic treatments, such as insulin, sulfonylureas (SUs), pioglitazone, and dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined for their roles in cancer biology, though findings are often inconclusive. More recently, novel medications, like glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, have revolutionized DM management by not only improving glycemic control but also delivering substantial cardiovascular and renal benefits. Given their diverse metabolic effects, including anti-obesogenic properties, these novel agents are now under meticulous investigation for their potential influence on tumorigenesis and cancer advancement. This review aims to offer a comprehensive exploration of the evolving landscape of glucose-lowering treatments and their implications in cancer biology. It critically evaluates experimental evidence surrounding the molecular mechanisms by which these medications may modulate oncogenic signaling pathways and reshape the tumor microenvironment (TME). Furthermore, it assesses translational research and clinical trials to gauge the practical relevance of these findings in real-world settings. Finally, it explores the potential of anti-diabetic medications as adjuncts in cancer treatment, particularly in enhancing the efficacy of chemotherapy, minimizing toxicity, and addressing resistance within the framework of immunotherapy.https://www.mdpi.com/2218-273X/14/11/1479cancerchronic low-grade inflammationdiabetes mellitusdoxorubicin-induced cardiomyopathyGLP-1 receptor agonistsimmune check point inhibitors
spellingShingle Dimitris Kounatidis
Natalia G. Vallianou
Irene Karampela
Eleni Rebelos
Marina Kouveletsou
Vasileios Dalopoulos
Petros Koufopoulos
Evanthia Diakoumopoulou
Nikolaos Tentolouris
Maria Dalamaga
Anti-Diabetic Therapies and Cancer: From Bench to Bedside
Biomolecules
cancer
chronic low-grade inflammation
diabetes mellitus
doxorubicin-induced cardiomyopathy
GLP-1 receptor agonists
immune check point inhibitors
title Anti-Diabetic Therapies and Cancer: From Bench to Bedside
title_full Anti-Diabetic Therapies and Cancer: From Bench to Bedside
title_fullStr Anti-Diabetic Therapies and Cancer: From Bench to Bedside
title_full_unstemmed Anti-Diabetic Therapies and Cancer: From Bench to Bedside
title_short Anti-Diabetic Therapies and Cancer: From Bench to Bedside
title_sort anti diabetic therapies and cancer from bench to bedside
topic cancer
chronic low-grade inflammation
diabetes mellitus
doxorubicin-induced cardiomyopathy
GLP-1 receptor agonists
immune check point inhibitors
url https://www.mdpi.com/2218-273X/14/11/1479
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