Xu Yuan-Rui, Wang An-Long, Li Ya-Qing
The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China.
Front Oncol. 2022 Oct 21;12:984525. doi: 10.3389/fonc.2022.984525. eCollection 2022.
Patients with chronic obstructive pulmonary disease (COPD), irrespective of their smoking history, are more likely to develop lung cancer than the general population. This is mainly because COPD is characterized by chronic persistent inflammation and hypoxia, which are the risk factors for lung cancer. However, the mechanisms underlying this observation are still unknown. Hypoxia-inducible factor 1-alpha (HIF-1α) plays an important role in the crosstalk that exists between inflammation and hypoxia. Furthermore, HIF-1α is the main regulator of somatic adaptation to hypoxia and is highly expressed in hypoxic environments. In this review, we discuss the molecular aspects of the crosstalk between hypoxia and inflammation, showing that HIF-1α is an important signaling pathway that drives COPD progression to lung cancer. Here, we also provide an overview of HIF-1α and its principal regulatory mechanisms, briefly describe HIF-1α-targeted therapy in lung cancer, and summarize substances that may be used to target HIF-1α at the level of COPD-induced inflammation.
慢性阻塞性肺疾病（COPD）患者，无论其吸烟史如何，相较于普通人群，患肺癌的可能性更高。这主要是因为COPD的特征是慢性持续性炎症和缺氧，而这两者都是肺癌的危险因素。然而，这一现象背后的机制仍不明确。缺氧诱导因子1α（HIF-1α）在炎症与缺氧之间的相互作用中发挥着重要作用。此外，HIF-1α是机体适应缺氧的主要调节因子，在缺氧环境中高表达。在本综述中，我们探讨了缺氧与炎症相互作用的分子层面，表明HIF-1α是驱动COPD进展为肺癌的重要信号通路。在此，我们还概述了HIF-1α及其主要调节机制，简要描述了肺癌中针对HIF-1α的治疗方法，并总结了在COPD诱导的炎症水平上可能用于靶向HIF-1α的物质。
