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Hippo 通路在非小细胞肺癌中的作用机制、潜在靶点和生物标志物。

Hippo pathway in non-small cell lung cancer: mechanisms, potential targets, and biomarkers.

机构信息

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Cancer Gene Ther. 2024 May;31(5):652-666. doi: 10.1038/s41417-024-00761-z. Epub 2024 Mar 18.

Abstract

Lung cancer is the primary contributor to cancer-related deaths globally, and non-small cell lung cancer (NSCLC) constitutes around 85% of all lung cancer cases. Recently, the emergence of targeted therapy and immunotherapy revolutionized the treatment of NSCLC and greatly improved patients' survival. However, drug resistance is inevitable, and extensive research has demonstrated that the Hippo pathway plays a crucial role in the development of drug resistance in NSCLC. The Hippo pathway is a highly conserved signaling pathway that is essential for various biological processes, including organ development, maintenance of epithelial balance, tissue regeneration, wound healing, and immune regulation. This pathway exerts its effects through two key transcription factors, namely Yes-associated protein (YAP) and transcriptional co-activator PDZ-binding motif (TAZ). They regulate gene expression by interacting with the transcriptional-enhanced associate domain (TEAD) family. In recent years, this pathway has been extensively studied in NSCLC. The review summarizes a comprehensive overview of the involvement of this pathway in NSCLC, and discusses the mechanisms of drug resistance, potential targets, and biomarkers associated with this pathway in NSCLC.

摘要

肺癌是全球癌症相关死亡的主要原因,而非小细胞肺癌(NSCLC)约占所有肺癌病例的 85%。近年来,靶向治疗和免疫疗法的出现彻底改变了 NSCLC 的治疗方法,极大地提高了患者的生存率。然而,耐药性是不可避免的,广泛的研究表明 Hippo 通路在 NSCLC 耐药性的发展中起着关键作用。Hippo 通路是一条高度保守的信号通路,对于各种生物学过程至关重要,包括器官发育、上皮平衡维持、组织再生、伤口愈合和免疫调节。该通路通过两个关键的转录因子 Yes 相关蛋白(YAP)和转录共激活因子 PDZ 结合基序(TAZ)发挥作用,它们通过与转录增强相关结构域(TEAD)家族相互作用来调节基因表达。近年来,该通路在 NSCLC 中的研究得到了广泛的关注。本综述全面概述了该通路在 NSCLC 中的作用,并讨论了与该通路相关的耐药机制、潜在靶点和生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/11101353/a32ace543180/41417_2024_761_Fig1_HTML.jpg

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