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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.  \n1 Department of Immunology, School of Medicine, Konkuk University, Chungju 27478, Republic of Korea; [sunhwang@kku.ac.kr](sunhwang@kku.ac.kr) (S.H.)  \n2 Research Institute of Medical Science, KU Open Innovation Center, Chungju 27478, Republic of Korea  \n3 Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea  \n4 Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea  \n* Correspondence: [smjeong@catholic.ac.kr](smjeong@catholic.ac.kr); Tel.: +82-2-3147-8336  \nSimple Summary  \nObesity is a growing global health problem that affects not only general health but also cancer risk and treatment outcomes. People with obesity are more likely to develop certain cancers, and their tumors often respond less effectively to therapy. This is partly because excess body fat alters the microenvironment around tumors, changes how cancer cells use energy, and alters abnormal adipose tissue-derived signals that promote tumor growth. In this review, we summarize how these obesity-related changes contribute to cancer progression and treatment resistance, and we discuss potential strategies to improve therapy. A better understanding of these mechanisms may support the development of more effective treatments for patients with obesity-related cancers.  \nAbstract  \nObesity has risen to the forefront of global public health challenges, particularly due to its association with several chronic diseases. Its association with cancer has attracted significant research interest. The relationship between obesity and cancer is complex and profoundly influences tumorigenesis, cancer progression, metastasis, and therapeutic efficacy. This review provides the molecular basis of these interactions, elucidating how obesity triggers changes in the tumor microenvironment, disrupts metabolic pathways, and promotes inflammation. These factors facilitate cancer development and reduce the efficacy of treatments. By unraveling these mechanisms, we aim to identify therapeutic strategies that could mitigate obesity’s detrimental effects on cancer outcomes and contribute to the development of more effective strategies for managing obesity-related cancers.  \nKeywords: obesity; tumor progression; therapy resistance; tumor microenvironment; inflammation; metabolic reprogramming  \n1. Introduction  \nObesity is defined by the World Health Organization (WHO) as abnormal or excessive fat accumulation that presents a risk to health, conventionally assessed by a body mass index (BMI) ≥ 30 kg/m2. This definition emphasizes excessive adipose tissue accumulation—particularly visceral fat—as the central pathophysiological feature linking  \nobesity to its downstream metabolic and inflammatory consequences, which are discussed in subsequent sections.  \nConceptually, obesity contributes to cancer through many of the established hallmarksof cancer [1,2] . The hallmarks most strongly affected by obesity include sustaining proliferative signaling and resisting cell death, driven by chronic activation of insulin/IGF-1 and adipokine-mediated pathways; deregulating cellular energetics, through systemic and local metabolic reprogramming; tumor-promoting inflammation, mediated by adipose tissue-derived cytokines; genome instability, due to oxidative stress and impaired DNA repair; and avoiding immune destruction, through obesity-driven immunosu","cbCaiqyO717tOeHl","https://ap.wps.com/l/cbCaiqyO717tOeHl","pdf",11708153,22,"English","# Simple Summary\n# Abstract\n# Keywords\n# 1. Introduction\n## Obesity definition and metabolic/inflammatory consequences\n## Hallmarks of cancer influenced by obesity\n## Metaflammation as a bridging concept\n## Global prevalence and health impact\n## Obesity–cancer relationship and clinical outcomes","[{\"question\":\"How does obesity affect cancer risk and outcomes?\",\"answer\":\"Obesity is associated with higher likelihood of developing certain cancers and with increased recurrence and mortality among cancer survivors. The review links these effects to changes in cellular and molecular pathways.\"},{\"question\":\"What mechanisms connect obesity to cancer progression?\",\"answer\":\"The review explains that obesity alters the tumor microenvironment, disrupts metabolic pathways, and promotes inflammation. It also discusses chronic immune and metabolic interactions that support tumor-promoting processes.\"},{\"question\":\"What is metaflammation in the context of obesity and cancer?\",\"answer\":\"Metaflammation refers to chronic, low-grade, metabolically driven inflammation characteristic of obesity. The review positions it as a bridge between obesity-related metabolic dysregulation and tumor-promoting inflammation.\"}]","Understanding the Interplay Between Obesity and Cancer - From Mechanisms to Therapeutic Opportunities | PDF",1790127820,55]