Rembiałkowska Nina, Kocik Zofia, Kłosińska Amelia, Kübler Maja, Pałkiewicz Agata, Rozmus Weronika, Sędzik Mikołaj, Wojciechowska Helena, Gajewska-Naryniecka Agnieszka
Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Pharmaceuticals (Basel). 2025 Sep 18;18(9):1406. doi: 10.3390/ph18091406.
Chronic inflammation, while originally a protective physiological response, is increasingly recognized as a key contributor to carcinogenesis. Prolonged inflammatory signaling leads to the sustained production of reactive oxygen and nitrogen species (ROS/RNS), resulting in direct and indirect DNA damage, including base modifications, strand breaks, and DNA cross-linking. Simultaneously, pro-inflammatory mediators such as NF-κB, IL-6, and TNF-α can interfere with DNA repair mechanisms, altering the efficiency of key pathways such as base excision and mismatch repair. Immune cells infiltrating chronically inflamed tissues, including macrophages and neutrophils, further exacerbate genomic instability through ROS/RNS release and cytokine production, creating a tumor-promoting microenvironment. Additionally, chronic inflammation has been implicated in the development of resistance to chemotherapy and radiotherapy by modulating DNA damage response pathways. Understanding the interplay between inflammation, genomic instability, and therapy resistance provides a framework for novel treatment strategies. Targeting chronic inflammation with non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or biological agents such as monoclonal antibodies offers promising avenues for cancer prevention and treatment. Targeting inflammation with NSAIDs, corticosteroids, and monoclonal antibodies shows promise in cancer prevention and therapy, particularly in lung and pancreatic cancer. These agents act by blocking key inflammatory pathways like COX-2, NF-κB, and cytokine signaling. However, potential adverse effects require further clinical evaluation.
慢性炎症虽然最初是一种保护性生理反应，但如今越来越被认为是致癌作用的关键促成因素。长期的炎症信号传导会导致活性氧和氮物种（ROS/RNS）持续产生，从而造成直接和间接的DNA损伤，包括碱基修饰、链断裂和DNA交联。同时，诸如核因子-κB（NF-κB）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）等促炎介质会干扰DNA修复机制，改变碱基切除和错配修复等关键途径的效率。浸润慢性炎症组织的免疫细胞，包括巨噬细胞和中性粒细胞，通过释放ROS/RNS和产生细胞因子进一步加剧基因组不稳定，营造出促肿瘤的微环境。此外，慢性炎症通过调节DNA损伤反应途径与化疗和放疗耐药性的发展有关。了解炎症、基因组不稳定和治疗耐药性之间的相互作用为新的治疗策略提供了一个框架。用非甾体抗炎药（NSAIDs）、皮质类固醇或单克隆抗体等生物制剂靶向慢性炎症为癌症预防和治疗提供了有前景的途径。用NSAIDs、皮质类固醇和单克隆抗体靶向炎症在癌症预防和治疗中显示出前景，尤其是在肺癌和胰腺癌中。这些药物通过阻断关键的炎症途径如环氧化酶-2（COX-2）、NF-κB和细胞因子信号传导起作用。然而，潜在的不良反应需要进一步的临床评估。
