Anand Shrikirti, Patel Trupti N
Department of Integrative Biology, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India.
Discov Oncol. 2024 Dec 18;15(1):779. doi: 10.1007/s12672-024-01662-1.
The progressive globalization of sedentary lifestyles and diets rich in lipids and processed foods has caused two major public health hazards-diabetes and obesity. The strong interlink between obesity and type 2 diabetes mellitus and their combined burden encompass them into a single term 'Diabesity'. They have also been tagged as the drivers for the onset of cancer. The clinical association between diabetes, obesity, and several types of human cancer demands an assessment of vital junctions correlating the three. This review focuses on revisiting the molecular axis linking diabetes and obesity to cancer through pathways that get imbalanced owing to metabolic upheaval. We also attempt to describe the functional disruptions of DNA repair mechanisms due to overwhelming oxidative DNA damage caused by diabesity. Genomic instability, a known cancer hallmark results when DNA repair does not work optimally, and as will be inferred from this review the obtruded metabolic homeostasis in diabetes and obesity creates a favorable microenvironment supporting metabolic reprogramming and enabling malignancies. Altered molecular and hormonal landscapes in these two morbidities provide a novel connection between metabolomics and oncogenesis. Understanding various aspects of the tumorigenic process in diabesity-induced cancers might help in the discovery of new biomarkers and prompt targeted therapeutic interventions.
久坐不动的生活方式以及富含脂质和加工食品的饮食日益全球化，已造成两大主要公共卫生危害——糖尿病和肥胖症。肥胖症与2型糖尿病之间存在紧密联系，且二者共同构成的负担使它们被纳入“糖尿病型肥胖症”这一统称。它们还被视为癌症发病的驱动因素。糖尿病、肥胖症与几种人类癌症之间的临床关联，要求对将这三者联系起来的关键环节进行评估。本综述着重通过因代谢紊乱而失衡的途径，重新审视将糖尿病和肥胖症与癌症联系起来的分子轴。我们还试图描述糖尿病型肥胖症导致的严重氧化性DNA损伤所引起的DNA修复机制功能紊乱。当DNA修复无法正常发挥作用时，基因组不稳定这一已知的癌症特征就会出现，而从本综述可以推断，糖尿病和肥胖症中代谢稳态的紊乱会营造一个有利的微环境，支持代谢重编程并促成恶性肿瘤。这两种病症中分子和激素格局的改变，在代谢组学与肿瘤发生之间建立了一种新的联系。了解糖尿病型肥胖症诱发癌症过程中的各个方面，可能有助于发现新的生物标志物，并推动有针对性的治疗干预措施。
