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鼻咽癌发病机制及进展中的代谢重编程:分子机制与治疗意义

Metabolic reprogramming in the pathogenesis and progression of nasopharyngeal carcinoma: molecular mechanisms and therapeutic implications.

作者信息

Wang Hongli, Hu Jiandao, Zhou Weibang, Qian Aijuan

机构信息

Department of Otolaryngology, The Affiliated People's Hospital of Ningbo University Ningbo, Zhejiang, China.

出版信息

Am J Cancer Res. 2024 Aug 25;14(8):4049-4064. doi: 10.62347/VYAT9271. eCollection 2024.

Abstract

Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer with a complex etiology involving genetic predispositions, environmental factors, and Epstein-Barr virus (EBV) infection. Despite progress in radiotherapy and chemotherapy, the prognosis for advanced NPC is still unfavorable, prompting the need for innovative therapeutic approaches. Metabolic reprogramming plays a crucial role in the development and progression of NPC, marked by substantial changes in glycolysis, lipid, and amino acid metabolism. These alterations aid tumor cell proliferation, survival under stress, and immune evasion, with features such as enhanced aerobic glycolysis (Warburg effect) and shifts in lipid and amino acid pathways. Oncogenic drivers like MYC, RAS, EGFR, and the loss of tumor suppressors such as TP53 and PTEN, along with key signaling pathways including mTOR, AMPK, and HIF-1α, orchestrate these metabolic changes. This review discusses the molecular mechanisms of metabolic reprogramming in NPC and outlines potential therapeutic targets within these pathways. Advances in metabolic imaging and biomarker discovery are also enhancing the precision of diagnostics and treatment monitoring, fostering personalized medicine in NPC treatment. This manuscript aims to provide a detailed overview of the current research and its implications for improving NPC management and patient outcomes through targeted metabolic therapies.

摘要

鼻咽癌(NPC)是一种独特的头颈癌,其病因复杂,涉及遗传易感性、环境因素和爱泼斯坦-巴尔病毒(EBV)感染。尽管放疗和化疗取得了进展,但晚期鼻咽癌的预后仍然不佳,这促使人们需要创新的治疗方法。代谢重编程在鼻咽癌的发生和发展中起着关键作用,其特征是糖酵解、脂质和氨基酸代谢发生显著变化。这些改变有助于肿瘤细胞增殖、在应激下存活以及免疫逃逸,具有有氧糖酵解增强(瓦伯格效应)以及脂质和氨基酸途径改变等特征。MYC、RAS、EGFR等致癌驱动因子以及TP53和PTEN等肿瘤抑制因子的缺失,连同包括mTOR、AMPK和HIF-1α在内的关键信号通路,共同协调这些代谢变化。本综述讨论了鼻咽癌中代谢重编程的分子机制,并概述了这些途径中的潜在治疗靶点。代谢成像和生物标志物发现方面的进展也在提高诊断和治疗监测的准确性,促进鼻咽癌治疗的个性化医疗。本文旨在详细概述当前的研究及其通过靶向代谢疗法改善鼻咽癌管理和患者预后的意义。

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