Feng Qiyi, Xiao Kai
Precision Medicine Research Center, Sichuan Provincial Key Laboratory of Precision Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
Pharmaceutics. 2022 Dec 13;14(12):2787. doi: 10.3390/pharmaceutics14122787.
Lung cancer is a common malignancy worldwide, with high morbidity and mortality. Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor that not only regulates different hallmarks of cancer, such as tumorigenesis, cell proliferation, and metastasis but also regulates the occurrence and maintenance of cancer stem cells (CSCs). Abnormal STAT3 activity has been found in a variety of cancers, including lung cancer, and its phosphorylation level is associated with a poor prognosis of lung cancer. Therefore, the STAT3 pathway may represent a promising therapeutic target for the treatment of lung cancer. To date, various types of STAT3 inhibitors, including natural compounds, small molecules, and gene-based therapies, have been developed through direct and indirect strategies, although most of them are still in the preclinical or early clinical stages. One of the main obstacles to the development of STAT3 inhibitors is the lack of an effective targeted delivery system to improve their bioavailability and tumor targetability, failing to fully demonstrate their anti-tumor effects. In this review, we will summarize the recent advances in STAT3 targeting strategies, as well as the applications of nanoparticle-mediated targeted delivery of STAT3 inhibitors in the treatment of lung cancer.
肺癌是全球常见的恶性肿瘤，发病率和死亡率都很高。信号转导及转录激活蛋白3（STAT3）是一种重要的转录因子，不仅调控肿瘤发生、细胞增殖和转移等不同的癌症特征，还调控癌症干细胞（CSC）的发生和维持。在包括肺癌在内的多种癌症中都发现了STAT3的异常活性，其磷酸化水平与肺癌的不良预后相关。因此，STAT3通路可能是治疗肺癌的一个有前景的治疗靶点。迄今为止，已通过直接和间接策略开发了各种类型的STAT3抑制剂，包括天然化合物、小分子和基于基因的疗法，尽管其中大多数仍处于临床前或临床早期阶段。开发STAT3抑制剂的主要障碍之一是缺乏有效的靶向递送系统来提高其生物利用度和肿瘤靶向性，无法充分发挥其抗肿瘤作用。在这篇综述中，我们将总结STAT3靶向策略的最新进展，以及纳米颗粒介导的STAT3抑制剂靶向递送在肺癌治疗中的应用。
