Yuan Weiwei, Shi Yin, Dai Shiping, Deng Mao, Zhu Kai, Xu Yuanmin, Chen Zhangming, Xu Zhou, Zhang Tianlong, Liang Song
Department of Thyroid Surgery, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China.
Department of Internal Medicine, Yiwu Maternity and Children Hospital, Yiwu, Zhejiang, China.
J Transl Med. 2024 Dec 24;22(1):1142. doi: 10.1186/s12967-024-05998-8.
Gastric cancer remains a significant health burden globally, especially prevalent in Asian and European regions. Despite a notable decline in incidence in the United States and Western Europe over recent decades, the disease's persistence underscores the urgency for advanced research in its pathogenesis and treatment strategies. Central to this pursuit is the exploration of the mitogen-activated protein kinase (MAPK) pathway, a pivotal cellular mechanism implicated in the complex processes of gastric cancer development, including cellular proliferation, invasion, migration, and metastasis. The MAPK or extracellular signal-regulated kinase pathway serves as a crucial conduit for transmitting extracellular signals to elicit intracellular responses, with its signaling cascades subject to alterations due to genetic and epigenetic variations across various diseases, prominently cancer. This review delves into the intricate role of the MAPK signaling pathway in the pathogenesis of gastric cancer, drawing upon the most recent and critical studies that shed light on MAPK pathway alterations as a gateway to the disease. It highlights the pathway's involvement in Helicobacter pylori-mediated gastric carcinogenesis and the tumorigenic processes induced by the Epstein-Barr virus, showcasing the substantial influence of miRNAs and lncRNAs in modulating gastric cancer's biological properties through their interaction with the MAPK pathway. Furthermore, the review extends into the therapeutic arena, discussing the promising impacts of herbal medicines, MAPK pathway inhibitors, and immunosuppressants on mitigating gastric cancer's progression. Through an exhaustive examination of the MAPK pathway's multifaceted role in gastric cancer, from molecular crosstalks to therapeutic prospects, this review aspires to contribute to the ongoing efforts in understanding and combating this global health challenge, paving the way for novel therapeutic interventions and improved patient outcomes.
胃癌仍然是全球一项重大的健康负担,在亚洲和欧洲地区尤为普遍。尽管近几十年来美国和西欧的发病率显著下降,但该疾病的持续存在凸显了对其发病机制和治疗策略进行深入研究的紧迫性。这一研究的核心是探索丝裂原活化蛋白激酶(MAPK)通路,这是一种关键的细胞机制,参与胃癌发展的复杂过程,包括细胞增殖、侵袭、迁移和转移。MAPK或细胞外信号调节激酶通路是将细胞外信号传递以引发细胞内反应的关键途径,其信号级联会因各种疾病(尤其是癌症)中的基因和表观遗传变异而发生改变。本综述深入探讨了MAPK信号通路在胃癌发病机制中的复杂作用,借鉴了最新的关键研究,这些研究揭示了MAPK通路改变是导致该疾病的一个途径。它强调了该通路在幽门螺杆菌介导的胃癌发生以及爱泼斯坦-巴尔病毒诱导的致瘤过程中的作用,展示了微小RNA(miRNA)和长链非编码RNA(lncRNA)通过与MAPK通路相互作用对调节胃癌生物学特性的重大影响。此外,综述还延伸到治疗领域,讨论了草药、MAPK通路抑制剂和免疫抑制剂对减轻胃癌进展的潜在影响。通过详尽考察MAPK通路在胃癌中从分子相互作用到治疗前景的多方面作用,本综述旨在为理解和应对这一全球健康挑战的持续努力做出贡献,为新的治疗干预措施和改善患者预后铺平道路。