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 (TERT). Several mechanisms of telomerase reactivation have been described in a variety of cancer types, including TERT promoter mutation, epigenetic modifications via a TERT promoter, TERT amplification, and TERT 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 TERT activates telomerase and determine its potential clinical application in NSCLC. More importantly, current treatment strategies targeting TERT in NSCLC have been summarized with the aim to promote discovery of novel strategies for the future treatment of NSCLC.

中文翻译：

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TERT 的致瘤作用及其在 NSCLC 中的潜在治疗靶点（综述）。

非小细胞肺癌 (NSCLC) 约占所有肺癌病例的 85%，通常在晚期被诊断出来，并且患者死亡率很高。尽管治疗策略的可用性越来越高，但 NSCLC 患者的预后仍然很差，5 年生存率较低。这种不良预后可能与非小细胞肺癌的肿瘤异质性及其对治疗药物的获得性和内在耐药性有关。有人提出，端粒酶抑制剂联合治疗可能是治疗药物敏感型和耐药型癌症的有效策略。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，这是由端粒酶逆转录酶的上调驱动的。叔）。端粒酶再激活的几种机制已在多种癌症类型中得到描述，包括TERT启动子突变、通过TERT启动子进行的表观遗传修饰、TERT扩增和TERT重排。本研究的目的是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TERT激活端粒酶的潜在机制并确定其在NSCLC中的潜在临床应用。更重要的是，目前针对TERT 的治疗策略 在 NSCLC 中进行了总结，目的是促进发现未来治疗 NSCLC 的新策略。