组蛋白去乙酰化酶抑制剂治疗致命肺癌的疗效。

2区 医学 Q1 Medicine Advances in Cancer Research Pub Date : 2023-01-01 DOI:10.1016/bs.acr.2022.12.003
Shabir Ahmad Ganai, Basit Amin Shah, Manzoor Ahmad Yatoo
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引用次数: 0

摘要

肺癌细胞对表皮生长因子受体(EGFR)、KRAS和Janus激酶2 (JAK2)定向治疗产生的严重耐药机制强烈地优先考虑对完全耐受、潜在细胞毒性和可以恢复肺癌细胞药物敏感性的新疗法的需求。修饰核小体整合组蛋白底物的翻译后修饰的酶蛋白正在成为击败各种恶性肿瘤的当前靶标。组蛋白去乙酰化酶(hdac)在多种肺癌类型中高表达。通过HDAC抑制剂(HDACi)阻断这些乙酰化橡皮擦的活性口袋已经成为消灭肺癌的一种乐观的治疗手段。本文首先概述了肺癌的统计数据和主要肺癌类型。在此基础上,简要介绍了传统疗法及其严重缺陷。然后,详细介绍了经典hdac的罕见表达与肺癌发病和扩展的关系。此外,本文深入讨论了HDACi在侵袭性肺癌中的单药作用,并重点介绍了这些抑制剂抑制或诱导的各种分子靶点,以产生细胞毒性作用。最特别的是,将这些抑制剂与其他治疗分子协同使用所产生的药理学效应以及由此改变的与癌症相关的途径被描述。进一步提高疗效的积极方向和全面临床评估的迫切要求已成为新的重点。
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Histone deacetylase inhibitors as sanguine epitherapeutics against the deadliest lung cancer.

The back-breaking resistance mechanisms generated by lung cancer cells against epidermal growth factor receptor (EGFR), KRAS and Janus kinase 2 (JAK2) directed therapies strongly prioritizes the requirement of novel therapies which are perfectly tolerated, potentially cytotoxic and can reinstate the drug-sensitivity in lung cancer cells. Enzymatic proteins modifying the post-translational modifications of nucleosome-integrated histone substrates are appearing as current targets for defeating various malignancies. Histone deacetylases (HDACs) are hyperexpressed in diverse lung cancer types. Blocking the active pocket of these acetylation erasers through HDAC inhibitors (HDACi) has come out as an optimistic therapeutic recourse for annihilating lung cancer. This article in the beginning gives an overview about lung cancer statistics and predominant lung cancer types. Succeeding this, compendium about conventional therapies and their serious drawbacks has been provided. Then, connection of uncommon expression of classical HDACs in lung cancer onset and expansion has been detailed. Moreover, keeping the main theme in view this article deeply discusses HDACi in the context of aggressive lung cancer as single agents and spotlights various molecular targets suppressed or induced by these inhibitors for engendering cytotoxic effect. Most particularly, the raised pharmacological effects achieved on using these inhibitors in concerted form with other therapeutic molecules and the cancer-linked pathways altered by this procedure are described. The positive direction towards further heightening of efficacy and the pressing requirement of exhaustive clinical assessment has been proposed as a new focus point.

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来源期刊
Advances in Cancer Research
Advances in Cancer Research 医学-肿瘤学
CiteScore
10.00
自引率
0.00%
发文量
52
期刊介绍: Advances in Cancer Research (ACR) has covered a remarkable period of discovery that encompasses the beginning of the revolution in biology. Advances in Cancer Research (ACR) has covered a remarkable period of discovery that encompasses the beginning of the revolution in biology. The first ACR volume came out in the year that Watson and Crick reported on the central dogma of biology, the DNA double helix. In the first 100 volumes are found many contributions by some of those who helped shape the revolution and who made many of the remarkable discoveries in cancer research that have developed from it.
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