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和及其在非小细胞肺癌中的潜在治疗靶点的致瘤作用(综述)。

Tumorigenic effect of and its potential therapeutic target in NSCLC (Review).

机构信息

Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434023, P.R. China.

Laboratory of Oncology, Center for Molecular Medicine, Yangtze University, Jingzhou, Hubei 434023, P.R. China.

出版信息

Oncol Rep. 2021 Aug;46(2). doi: 10.3892/or.2021.8133. Epub 2021 Jul 19.

Abstract

Non‑small cell lung cancer (NSCLC), which accounts for ~85% of all lung cancer cases, is commonly diagnosed at an advanced stage and has a high patient mortality rate. Despite the increasing availability of treatment strategies, the prognosis of patients with NSCLC remains poor, with a low 5‑year survival rate. This poor prognosis may be associated with the tumor heterogeneity of NSCLC, as well as its acquisition and intrinsic resistance to therapeutic drugs. It has been suggested that combination therapy with telomerase inhibition may be an effective strategy for the treatment of drug‑sensitive and drug‑resistant types of cancer. Telomerase is the key enzyme for cell survival, and ~90% of human cancers maintain telomeres by activating telomerase, which is driven by the upregulation of telomerase reverse transcriptase (). Several mechanisms of telomerase reactivation have been described in a variety of cancer types, including promoter mutation, epigenetic modifications via a promoter, amplification, and rearrangement. The aim of the present study was to comprehensively review telomerase activity and its association with the clinical characteristics and prognosis of NSCLC, as well as analyze the potential mechanism via which activates telomerase and determine its potential clinical application in NSCLC. More importantly, current treatment strategies targeting in NSCLC have been summarized with the aim to promote discovery of novel strategies for the future treatment of NSCLC.

摘要

非小细胞肺癌(NSCLC)约占所有肺癌病例的 85%,通常在晚期诊断,患者死亡率高。尽管治疗策略的可及性不断增加,但 NSCLC 患者的预后仍然较差,5 年生存率低。这种不良预后可能与 NSCLC 的肿瘤异质性以及对治疗药物的获得性和内在耐药性有关。有人提出,端粒酶抑制联合治疗可能是治疗耐药和敏感型癌症的有效策略。端粒酶是细胞存活的关键酶,约 90%的人类癌症通过激活端粒酶来维持端粒,端粒酶由端粒酶逆转录酶()的上调驱动。在多种癌症类型中已经描述了端粒酶重新激活的几种机制,包括启动子突变、通过启动子的表观遗传修饰、扩增和重排。本研究旨在全面回顾端粒酶活性及其与 NSCLC 临床特征和预后的关系,并分析通过激活端粒酶的潜在机制,以及确定其在 NSCLC 中的潜在临床应用。更重要的是,总结了针对 NSCLC 中 的当前治疗策略,旨在促进未来 NSCLC 治疗新策略的发现。

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