Parakh Sagun, Ernst Matthias, Poh Ashleigh R
Department of Medical Oncology, The Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, VIC 3084, Australia.
Tumor Targeting Laboratory, The Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
Cancers (Basel). 2021 Dec 11;13(24):6228. doi: 10.3390/cancers13246228.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 85% of lung cancer cases. Aberrant activation of the Signal Transducer and Activator of Transcription 3 (STAT3) is frequently observed in NSCLC and is associated with a poor prognosis. Pre-clinical studies have revealed an unequivocal role for tumor cell-intrinsic and extrinsic STAT3 signaling in NSCLC by promoting angiogenesis, cell survival, cancer cell stemness, drug resistance, and evasion of anti-tumor immunity. Several STAT3-targeting strategies have also been investigated in pre-clinical models, and include preventing upstream receptor/ligand interactions, promoting the degradation of STAT3 mRNA, and interfering with STAT3 DNA binding. In this review, we discuss the molecular and immunological mechanisms by which persistent STAT3 activation promotes NSCLC development, and the utility of STAT3 as a prognostic and predictive biomarker in NSCLC. We also provide a comprehensive update of STAT3-targeting therapies that are currently undergoing clinical evaluation, and discuss the challenges associated with these treatment modalities in human patients.
非小细胞肺癌（NSCLC）是最常见的肺癌类型，占肺癌病例的85%。信号转导子和转录激活子3（STAT3）的异常激活在NSCLC中经常被观察到，并且与预后不良相关。临床前研究已经揭示了肿瘤细胞内在和外在的STAT3信号在NSCLC中通过促进血管生成、细胞存活、癌细胞干性、耐药性和逃避抗肿瘤免疫方面具有明确的作用。在临床前模型中也研究了几种靶向STAT3的策略，包括阻止上游受体/配体相互作用、促进STAT3 mRNA的降解以及干扰STAT3与DNA的结合。在这篇综述中，我们讨论了持续的STAT3激活促进NSCLC发展的分子和免疫机制，以及STAT3作为NSCLC预后和预测生物标志物的效用。我们还全面更新了目前正在进行临床评估的靶向STAT3疗法，并讨论了这些治疗方式在人类患者中面临的挑战。
