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The Role of Insulin Resistance in Cancer. Curr. Oncol. 2025, 32, 477. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/curroncol32090477](10.3390/curroncol32090477)  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \nJefferson Einstein Montgomery Hospital, 559 West Germantown Pike, East Norriton, PA 19403, USA;  \n[cbhimineni@gmail.com](cbhimineni@gmail.com) (C.B.); [shivani.modi@jefferson.edu](shivani.modi@jefferson.edu) (S.M.); [j.atousa@gmail.com](j.atousa@gmail.com) (A.J.);  \n[quiza.katherine@mayo.edu](quiza.katherine@mayo.edu) (K.Q.)  \n* Correspondence: [daniel.bitetto@jefferson.edu](daniel.bitetto@jefferson.edu)  \nSimple Summary  \nInsulin resistance is a condition, common in obesity and type 2 diabetes, where the body’s cells do not respond properly to insulin, a hormone that controls blood sugar. This review explains how this metabolic problem is a significant risk factor for several major cancers, including those of the breast, liver, and endometrium. The high levels of insulin, chronic inflammation, and altered cellular energy usage associated with insulin resistance create an environment that can fuel the growth and spread of tumors. Since insulin resistance is a modifiable condition, understanding this link opens up new strategies for cancer prevention and treatment, emphasizing the importance of lifestyle interventions and metabolic health.  \nAbstract  \nInsulin resistance (IR) is a prevalent metabolic condition characterized by reduced cellular responsiveness to insulin and consequent hyperinsulinemia, and it is a key component of type 2 diabetes and metabolic syndrome. A growing body of evidence suggests IR is a critical accomplice in the pathogenesis of various cancers. This review synthesizes evidence on underlying molecular mechanisms, including the integrated roles of the insulin/IGF system, chronic inflammation, metabolic reprogramming, and mitochondrial dysfunction. This review proposes that metabolic dysregulation should be viewed as a modifiable oncogenic force. This perspective illuminates new pathways for understanding cancer development and offers promising avenues for prevention and therapeutic intervention.  \nKeywords: insulin resistance; obesity; breast cancer; colorectal cancer; endometrial cancer; liver cancer; pancreatic cancer  \n1. Introduction  \nInsulin resistance (IR) is a pathological condition in which the body’s cells become less responsive to the action of insulin, leading to elevated blood insulin levels. Traditionally associated with type 2 diabetes, obesity, and metabolic syndrome, insulin resistance has gained significant attention for its potential role in cancer development and progression. Insulin, along with insulin-like growth factors (IGFs), is involved in regulating cell growth, metabolism, and survival. Given that cancer is fundamentally a disease of dysregulated cell growth, the potential connection between insulin resistance and cancer has become a focal point of research. This review will examine the evidence supporting the link between insulin resistance and cancer, explore the underlying pathophysiology, and discuss the clinical implications for cancer prevention and treatment.  \nThe relationship between metabolic disorders and cancer has been known for over 100 years and represents a significant public health challenge [","cbCaib19jEo23nIH","https://ap.wps.com/l/cbCaib19jEo23nIH","pdf",281813,"English","# Simple Summary\n# Abstract\n# Introduction\n# Search Strategy\n# Core Molecular Mechanisms Linking Insulin Resistance and Cancer","[{\"question\":\"What is insulin resistance and why is it important in cancer risk?\",\"answer\":\"Insulin resistance is reduced responsiveness of cells to insulin, leading to elevated blood insulin. The review explains that this metabolic state is a significant risk factor for several cancers, including breast, liver, and endometrial cancers.\"},{\"question\":\"What molecular mechanisms connect insulin resistance to cancer?\",\"answer\":\"The review synthesizes evidence involving the insulin/IGF system, chronic inflammation, metabolic reprogramming, and mitochondrial dysfunction. These processes are described as interconnected and reinforcing tumor-promoting conditions.\"},{\"question\":\"Why does the review emphasize insulin resistance as a modifiable target?\",\"answer\":\"Because insulin resistance can be improved through lifestyle and metabolic-health interventions, the review argues it can support new prevention and treatment strategies. It frames metabolic dysregulation as a modifiable oncogenic force.\"}]","The Role of Insulin Resistance in Cancer - Review | PDF",1790202447,28]