Exploring the Role of Hypoxia and HIF-1α in the Intersection of Type 2 Diabetes Mellitus and Endometrial Cancer.

IF 2.8 4区 医学 Q2 ONCOLOGY
Alagappan V S Geetha, Kannan Harithpriya, Kumar Ganesan, Kunka Mohanram Ramkumar
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Abstract

Diabetes and Cancer are the most complex chronic diseases, accounting for significant global mortality and morbidity. The association between Type 2 DM (T2DM) and endometrial cancer (EC) is multifaced, sharing numerous risk factors, including insulin resistance, obesity, hypoxia, and oxidative stress. Hypoxia plays a vital role in T2DM pathogenesis by altering the insulin level and pancreatic β-cell failure through an imbalance between antioxidant enzymes and cellular oxidative levels, while chronic inflammation contributes to EC malignancy. HIF-1α is a potent transcription factor involved in modulating cellular responses to hypoxia within the disease environment. Targeting the HIF-1α signaling cascade, a major metabolic regulator may contribute to advanced therapeutic advances. This review focuses on the association between T2DM and EC, especially focusing on hypoxia and HIF signaling pathways. These intersect with key pathways involved in T2DM and EC pathology, such as insulin signaling, PI3K/AKT, mTOR pathway, MUC1/HIF-1α pathway, and hormonal imbalance. Understanding this complex relationship paves the way for future researchers to develop HIF-1α-targeted therapies that could lead to novel combination therapies to treat these comorbid conditions.

探讨缺氧和HIF-1α在2型糖尿病和子宫内膜癌交叉中的作用。
糖尿病和癌症是最复杂的慢性病,占全球死亡率和发病率的重要比例。2型糖尿病(T2DM)和子宫内膜癌(EC)之间的关系是多方面的,有许多危险因素,包括胰岛素抵抗、肥胖、缺氧和氧化应激。缺氧通过抗氧化酶和细胞氧化水平失衡改变胰岛素水平和胰腺β细胞衰竭,在T2DM发病中起重要作用,而慢性炎症有助于EC恶性肿瘤的发生。HIF-1α是一种有效的转录因子,参与调节疾病环境中细胞对缺氧的反应。针对HIF-1α信号级联,一种主要的代谢调节剂可能有助于先进的治疗进展。本文综述了T2DM与EC之间的关系,特别是缺氧和HIF信号通路。这些与T2DM和EC病理相关的关键通路交叉,如胰岛素信号、PI3K/AKT、mTOR通路、MUC1/HIF-1α通路和激素失衡。了解这种复杂的关系为未来的研究人员开发hif -1α靶向疗法铺平了道路,这种疗法可能会导致新的联合疗法来治疗这些合并症。
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来源期刊
Current oncology
Current oncology ONCOLOGY-
CiteScore
3.30
自引率
7.70%
发文量
664
审稿时长
1 months
期刊介绍: Current Oncology is a peer-reviewed, Canadian-based and internationally respected journal. Current Oncology represents a multidisciplinary medium encompassing health care workers in the field of cancer therapy in Canada to report upon and to review progress in the management of this disease. We encourage submissions from all fields of cancer medicine, including radiation oncology, surgical oncology, medical oncology, pediatric oncology, pathology, and cancer rehabilitation and survivorship. Articles published in the journal typically contain information that is relevant directly to clinical oncology practice, and have clear potential for application to the current or future practice of cancer medicine.
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