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肥胖-自噬-癌症轴:机制见解和治疗观点。

The obesity-autophagy-cancer axis: Mechanistic insights and therapeutic perspectives.

机构信息

Department of Human Anatomy and Cell Science, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada; Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Department of Biochemistry and Molecular Biology, School of Biology, Complutense University, Madrid, Spain; Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain.

出版信息

Semin Cancer Biol. 2024 Feb;99:24-44. doi: 10.1016/j.semcancer.2024.01.003. Epub 2024 Feb 1.

Abstract

Autophagy, a self-degradative process vital for cellular homeostasis, plays a significant role in adipose tissue metabolism and tumorigenesis. This review aims to elucidate the complex interplay between autophagy, obesity, and cancer development, with a specific emphasis on how obesity-driven changes affect the regulation of autophagy and subsequent implications for cancer risk. The burgeoning epidemic of obesity underscores the relevance of this research, particularly given the established links between obesity, autophagy, and various cancers. Our exploration delves into hormonal influence, notably INS (insulin) and LEP (leptin), on obesity and autophagy interactions. Further, we draw attention to the latest findings on molecular factors linking obesity to cancer, including hormonal changes, altered metabolism, and secretory autophagy. We posit that targeting autophagy modulation may offer a potent therapeutic approach for obesity-associated cancer, pointing to promising advancements in nanocarrier-based targeted therapies for autophagy modulation. However, we also recognize the challenges inherent to these approaches, particularly concerning their precision, control, and the dual roles autophagy can play in cancer. Future research directions include identifying novel biomarkers, refining targeted therapies, and harmonizing these approaches with precision medicine principles, thereby contributing to a more personalized, effective treatment paradigm for obesity-mediated cancer.

摘要

自噬是一种对细胞内稳态至关重要的自我降解过程,在脂肪组织代谢和肿瘤发生中起着重要作用。本综述旨在阐明自噬、肥胖和癌症发展之间的复杂相互作用,特别强调肥胖驱动的变化如何影响自噬的调节,以及对癌症风险的后续影响。肥胖症的流行突显了这项研究的相关性,特别是考虑到肥胖、自噬和各种癌症之间已经建立的联系。我们的探索深入探讨了激素(胰岛素和瘦素)对肥胖和自噬相互作用的影响。此外,我们还关注了将肥胖与癌症联系起来的最新分子因素的发现,包括激素变化、代谢改变和分泌自噬。我们假设,靶向自噬调节可能为肥胖相关癌症提供一种有效的治疗方法,指向基于纳米载体的靶向自噬调节治疗的有前途的进展。然而,我们也认识到这些方法所固有的挑战,特别是考虑到它们的精确性、控制性以及自噬在癌症中的双重作用。未来的研究方向包括确定新的生物标志物、完善靶向治疗,并将这些方法与精准医学原则相协调,从而为肥胖介导的癌症提供更个性化、更有效的治疗模式。

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