Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link

Obesity, a global health concern, is associated with severe health issues like type 2 diabetes, heart disease, and respiratory complications. It also increases the risk of various cancers, including melanoma, endometrial, prostate, pancreatic, esophageal adenocarcinoma, colorectal carcinoma, renal a...

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Main Authors: Alanoud Abdulla, Hana Q. Sadida, Jayakumar Jerobin, Imadeldin Elfaki, Rashid Mir, Sameer Mirza, Mayank Singh, Muzafar A. Macha, Shahab Uddin, Khalid Fakhro, Ajaz A. Bhat, Ammira S. Al-Shabeeb Akil
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Journal of the National Cancer Center
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667005424001029
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author Alanoud Abdulla
Hana Q. Sadida
Jayakumar Jerobin
Imadeldin Elfaki
Rashid Mir
Sameer Mirza
Mayank Singh
Muzafar A. Macha
Shahab Uddin
Khalid Fakhro
Ajaz A. Bhat
Ammira S. Al-Shabeeb Akil
author_facet Alanoud Abdulla
Hana Q. Sadida
Jayakumar Jerobin
Imadeldin Elfaki
Rashid Mir
Sameer Mirza
Mayank Singh
Muzafar A. Macha
Shahab Uddin
Khalid Fakhro
Ajaz A. Bhat
Ammira S. Al-Shabeeb Akil
author_sort Alanoud Abdulla
collection DOAJ
description Obesity, a global health concern, is associated with severe health issues like type 2 diabetes, heart disease, and respiratory complications. It also increases the risk of various cancers, including melanoma, endometrial, prostate, pancreatic, esophageal adenocarcinoma, colorectal carcinoma, renal adenocarcinoma, and pre-and post-menopausal breast cancer. Obesity-induced cellular changes, such as impaired CD8+ T cell function, dyslipidemia, hypercholesterolemia, insulin resistance, mild hyperglycemia, and fluctuating levels of leptin, resistin, adiponectin, and IL-6, contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes. Adipocytes release leptin, a pro-inflammatory substance that stimulates cancer cell proliferation, inflammation, and invasion, altering the tumor cell metabolic pathway. Adiponectin, an insulin-sensitizing adipokine, is typically downregulated in obese individuals. It has antiproliferative, proapoptotic, and antiangiogenic properties, making it a potential cancer treatment. This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer, drawing on an extensive, though non-systematic, survey of the recent literature. This approach allows us to integrate and synthesize findings from various studies, offering a cohesive perspective on emerging themes and potential therapeutic targets. The review explores the metabolic disturbances, cellular alterations, inflammatory responses, and shifts in the tumor microenvironment that contribute to the obesity-cancer link. Finally, it discusses potential therapeutic strategies aimed at disrupting these connections, offering valuable insights into future research directions and the development of targeted interventions.
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spelling doaj-art-64f8822f74334f9bb7cbee58bf46442a2025-08-20T03:12:35ZengElsevierJournal of the National Cancer Center2667-00542025-02-015182710.1016/j.jncc.2024.11.001Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer linkAlanoud Abdulla0Hana Q. Sadida1Jayakumar Jerobin2Imadeldin Elfaki3Rashid Mir4Sameer Mirza5Mayank Singh6Muzafar A. Macha7Shahab Uddin8Khalid Fakhro9Ajaz A. Bhat10Ammira S. Al-Shabeeb Akil11Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, QatarDepartment of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, QatarQatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi ArabiaDepartment of Medical Laboratory Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi ArabiaDepartment of Chemistry, College of Sciences, United Arab Emirates University, Al-Ain, United Arab EmiratesDepartment of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaWatson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Pulwama, Jammu and Kashmir, IndiaTranslational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar; Laboratory of Animal Research Center, Qatar University, Doha, QatarDepartment of Human Genetics, Sidra Medicine, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar; Department of Genetic Medicine, Weill Cornell Medicine, Doha, QatarDepartment of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, Qatar; Corresponding authors.Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, Qatar; Corresponding authors.Obesity, a global health concern, is associated with severe health issues like type 2 diabetes, heart disease, and respiratory complications. It also increases the risk of various cancers, including melanoma, endometrial, prostate, pancreatic, esophageal adenocarcinoma, colorectal carcinoma, renal adenocarcinoma, and pre-and post-menopausal breast cancer. Obesity-induced cellular changes, such as impaired CD8+ T cell function, dyslipidemia, hypercholesterolemia, insulin resistance, mild hyperglycemia, and fluctuating levels of leptin, resistin, adiponectin, and IL-6, contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes. Adipocytes release leptin, a pro-inflammatory substance that stimulates cancer cell proliferation, inflammation, and invasion, altering the tumor cell metabolic pathway. Adiponectin, an insulin-sensitizing adipokine, is typically downregulated in obese individuals. It has antiproliferative, proapoptotic, and antiangiogenic properties, making it a potential cancer treatment. This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer, drawing on an extensive, though non-systematic, survey of the recent literature. This approach allows us to integrate and synthesize findings from various studies, offering a cohesive perspective on emerging themes and potential therapeutic targets. The review explores the metabolic disturbances, cellular alterations, inflammatory responses, and shifts in the tumor microenvironment that contribute to the obesity-cancer link. Finally, it discusses potential therapeutic strategies aimed at disrupting these connections, offering valuable insights into future research directions and the development of targeted interventions.http://www.sciencedirect.com/science/article/pii/S2667005424001029ObesityCancer riskTumor microenvironmentInflammationTherapeutic interventionsGut microbiome
spellingShingle Alanoud Abdulla
Hana Q. Sadida
Jayakumar Jerobin
Imadeldin Elfaki
Rashid Mir
Sameer Mirza
Mayank Singh
Muzafar A. Macha
Shahab Uddin
Khalid Fakhro
Ajaz A. Bhat
Ammira S. Al-Shabeeb Akil
Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link
Journal of the National Cancer Center
Obesity
Cancer risk
Tumor microenvironment
Inflammation
Therapeutic interventions
Gut microbiome
title Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link
title_full Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link
title_fullStr Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link
title_full_unstemmed Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link
title_short Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link
title_sort unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity cancer link
topic Obesity
Cancer risk
Tumor microenvironment
Inflammation
Therapeutic interventions
Gut microbiome
url http://www.sciencedirect.com/science/article/pii/S2667005424001029
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