死亡配体受体（DLR）信号：其在癌症中的非凋亡功能和DLR定向治疗的后果。

IF 6.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Discovery Today Pub Date : 2025-02-01 DOI:10.1016/j.drudis.2025.104299

Khalid Rashid , Holger Kalthoff , Sarki A. Abdulkadir , Dieter Adam

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引用次数: 0

摘要

死亡配体（dl），特别是肿瘤坏死因子α (TNF-α)、FAS配体（FASL）和TNF相关的凋亡诱导配体（TRAIL），统称为TFT，是TNF超家族的关键成员。虽然传统上与细胞凋亡有关，但TFT蛋白已成为各种非细胞凋亡过程的关键调节因子。本文综述了TFT在肿瘤中的非凋亡功能，并探讨了其复杂的串扰信号通路及其对核因子κB （NF-κB）信号传导、炎症和促肿瘤功能的影响。它还强调了在将涉及dl的合成致命策略转化为临床应用方面存在的潜在联系和障碍。最后，它讨论了与针对恶性和非恶性疾病的tft靶向治疗策略相关的挑战和机遇。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Death ligand receptor (DLR) signaling: Its non-apoptotic functions in cancer and the consequences of DLR-directed therapies

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Death ligand receptor (DLR) signaling: Its non-apoptotic functions in cancer and the consequences of DLR-directed therapies

Death ligands (DLs), particularly tumor necrosis factor alpha (TNF-α), FAS ligand (FASL), and TNF-related apoptosis-inducing ligand (TRAIL), collectively termed TFT, are pivotal members of the TNF superfamily. While traditionally linked to apoptosis, TFT proteins have emerged as key regulators of various non-apoptotic processes. This review summarizes the non-apoptotic functions of TFT in cancer and explores the intricate crosstalk signaling pathways and their impact on nuclear factor kappa B (NF-κB) signaling, inflammation, and pro-tumorigenic function. It also highlights the potential connections and hurdles that exist in translating synthetic lethality strategies involving DLs into clinical applications. Lastly, it discusses the challenges and opportunities associated with TFT-targeted therapeutic strategies for both malignant and non-malignant diseases.

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来源期刊

Drug Discovery Today 医学-药学

CiteScore

14.80

自引率

2.70%

发文量

293

审稿时长

6 months

期刊介绍： Drug Discovery Today delivers informed and highly current reviews for the discovery community. The magazine addresses not only the rapid scientific developments in drug discovery associated technologies but also the management, commercial and regulatory issues that increasingly play a part in how R&D is planned, structured and executed. Features include comment by international experts, news and analysis of important developments, reviews of key scientific and strategic issues, overviews of recent progress in specific therapeutic areas and conference reports.