Prevalence of obesity, an established risk factor for many cancers, has increased dramatically over the past 50 years in the United States and across the globe. Relative to normoweight cancer patients, obese cancer patients often have poorer prognoses, resistance to chemotherapies, and are more likely to develop distant metastases. Recent progress on elucidating the mechanisms underlying the obesity-cancer connection suggests that obesity exerts pleomorphic effects on pathways related to tumor development and progression and, thus, there are multiple opportunities for primary prevention and treatment of obesity-related cancers. Obesity-associated alterations, including systemic metabolism, adipose inflammation, growth factor signaling, and angiogenesis, are emerging as primary drivers of obesity-associated cancer development and progression. These obesity-associated host factors interact with the intrinsic molecular characteristics of cancer cells, facilitating several of the hallmarks of cancer. Each is considered in the context of potential preventive and therapeutic strategies to reduce the burden of obesity-related cancers. In addition, this review focuses on emerging mechanisms behind the obesity-cancer link, as well as relevant dietary interventions, including calorie restriction, intermittent fasting, low-fat diet, and ketogenic diet, that are being implemented in preclinical and clinical trials, with the ultimate goal of reducing incidence and progression of obesity-related cancers.

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转化基于机制的策略来打破肥胖与癌症的联系：叙事回顾

肥胖是许多癌症的既定危险因素，过去 50 年来，肥胖的患病率在美国和全球范围内急剧增加。相对于正常体重的癌症患者，肥胖的癌症患者往往预后较差，对化疗有抵抗力，并且更有可能发生远处转移。阐明肥胖与癌症之间联系的机制的最新进展表明，肥胖对肿瘤发生和进展相关的途径产生多形性影响，因此，肥胖相关癌症的一级预防和治疗有多种机会。肥胖相关的改变，包括全身代谢、脂肪炎症、生长因子信号传导和血管生成，正在成为肥胖相关癌症发生和进展的主要驱动因素。这些与肥胖相关的宿主因子与癌细胞的内在分子特征相互作用，促进癌症的一些特征。每一种方法都在潜在的预防和治疗策略的背景下进行考虑，以减少肥胖相关癌症的负担。此外，本综述重点关注肥胖与癌症联系背后的新兴机制，以及相关的饮食干预措施，包括热量限制、间歇性禁食、低脂饮食和生酮饮食，这些干预措施正在临床前和临床试验中实施，最终目标是减少肥胖相关癌症的发病率和进展。