Department of Chemistry and Biochemistry and the BIO5 Institute, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States.
Laboratory of Cancer Immunometabolism, National Cancer Institute, Frederick, Maryland 21702, United States.
Inorg Chem. 2021 Nov 1;60(21):15941-15947. doi: 10.1021/acs.inorgchem.1c02434. Epub 2021 Oct 25.
The mechanistic roles of nitric oxide (NO) during cancer progression have been important considerations since its discovery as an endogenously generated free radical. Nonetheless, the impacts of this signaling molecule can be seemingly contradictory, being both pro-and antitumorigenic, which complicates the development of cancer treatments based on the modulation of NO fluxes in tumors. At a fundamental level, low levels of NO drive oncogenic pathways, immunosuppression, metastasis, and angiogenesis, while higher levels lead to apoptosis and reduced hypoxia and also sensitize tumors to conventional therapies. However, clinical outcome depends on the type and stage of the tumor as well as the tumor microenvironment. In this Viewpoint, the current understanding of the concentration, spatial, and temporal dependence of responses to NO is correlated with potential treatment and prevention technologies and strategies.
自一氧化氮（NO）被发现作为内源性自由基以来，其在癌症进展过程中的机械作用一直是重要的考虑因素。然而，这种信号分子的影响似乎相互矛盾，既具有促进肿瘤发生的作用，也具有抗肿瘤发生的作用，这使得基于调节肿瘤中 NO 通量的癌症治疗的发展变得复杂。在根本水平上，低水平的 NO 驱动致癌途径、免疫抑制、转移和血管生成，而更高水平的 NO 则导致细胞凋亡和减少缺氧，并使肿瘤对常规治疗更敏感。然而，临床结果取决于肿瘤的类型和阶段以及肿瘤微环境。在本观点中，与潜在的治疗和预防技术和策略相关，目前对 NO 反应的浓度、空间和时间依赖性的理解。
