The Department of Respiratory and Critical Medicine, Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.
Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Curr Drug Targets. 2022;23(13):1261-1276. doi: 10.2174/1389450123666220705123315.
Lung toxicity is a key limiting factor for cancer therapy, especially lung, breast, and esophageal malignancies. Radiotherapy for chest and breast malignancies can cause lung injury. However, systemic cancer therapy with chemotherapy may also induce lung pneumonitis and fibrosis. Radiotherapy produces reactive oxygen species (ROS) directly via interacting with water molecules within cells. However, radiation and other therapy modalities may induce the endogenous generation of ROS and nitric oxide (NO) by immune cells and some nonimmune cells such as fibroblasts and endothelial cells. There are several ROS generating enzymes within lung tissue. NADPH Oxidase enzymes, cyclooxygenase-2 (COX-2), dual oxidases (DUOX1 and DUOX2), and the cellular respiratory system in the mitochondria are the main sources of ROS production following exposure of the lung to anticancer agents. Furthermore, inducible nitric oxide synthase (iNOS) has a key role in the generation of NO following radiotherapy or chemotherapy. Continuous generation of ROS and NO by endothelial cells, fibroblasts, macrophages, and lymphocytes causes apoptosis, necrosis, and senescence, which lead to the release of inflammatory and pro-fibrosis cytokines. This review discusses the cellular and molecular mechanisms of redox-induced lung injury following cancer therapy and proposes some targets and perspectives to alleviate lung toxicity.
肺毒性是癌症治疗的一个关键限制因素，特别是肺癌、乳腺癌和食管癌。胸部和乳腺癌的放射治疗会导致肺损伤。然而，全身化疗等癌症治疗也可能导致肺肺炎和纤维化。放疗通过与细胞内的水分子直接相互作用产生活性氧（ROS）。然而，辐射和其他治疗方式可能会通过免疫细胞和一些非免疫细胞（如成纤维细胞和内皮细胞）诱导内源性 ROS 和一氧化氮（NO）的产生。肺组织内有几种产生 ROS 的酶。NADPH 氧化酶、环氧化酶-2（COX-2）、双氧化酶（DUOX1 和 DUOX2）和线粒体中的细胞呼吸系统是肺癌暴露于抗癌药物后产生 ROS 的主要来源。此外，诱导型一氧化氮合酶（iNOS）在放射治疗或化学治疗后产生 NO 中起关键作用。内皮细胞、成纤维细胞、巨噬细胞和淋巴细胞持续产生 ROS 和 NO，导致细胞凋亡、坏死和衰老，从而导致炎症和促纤维化细胞因子的释放。这篇综述讨论了癌症治疗后氧化还原诱导的肺损伤的细胞和分子机制，并提出了一些减轻肺毒性的靶点和观点。
