Dartmouth Hitchcock Medical Center, Comprehensive Thoracic Oncology Program, Norris Cotton Cancer Center, Lebanon, USA.
Expert Opin Biol Ther. 2011 Dec;11(12):1663-8. doi: 10.1517/14712598.2011.627850. Epub 2011 Oct 13.
Inflammatory pathways may be an important contributor to morbidity and mortality associated with lung cancer. The oncogene-associated inflammatory microenvironment leads to production of inflammatory cytokines such as IL-6. IL-6 is associated with poor prognosis and correlates with debilitating lung-cancer-related symptoms such as fatigue, thromboembolism, cachexia and anemia. IL-6 has been implicated in resistance of lung cancer to EGF inhibitors. A mAb therapy targeting IL-6 may be an effective treatment for the inflammatory microenvironment in lung cancer.
An understanding of the inflammatory pathways involved in lung cancer, including the central role of IL-6, and how inflammation affects the course and treatment of lung cancer. The mAb ALD518, which targets IL-6, and its investigational development and use in advanced NSCLC. Preclinical and Phase I and II studies of ALD518 with a focus on NSCLC. How ALD518 could be used in NSCLC in the future.
IL-6-mediated inflammation may contribute to NSCLC-related morbidity and mortality. In preclinical and Phase I and II trials ALD518 targeting IL-6 appears well tolerated and ameliorates NSCLC-related anemia and cachexia. Other clinical outcomes need further study, and may include effects on overall survival, hypercoagulability associated with lung cancer and decreased resistance to EGF-pathway inhibitors.
炎症途径可能是与肺癌相关发病率和死亡率的重要因素。致癌基因相关的炎症微环境导致炎症细胞因子的产生，如 IL-6。IL-6 与预后不良相关，并与肺癌相关的衰弱症状相关，如疲劳、血栓栓塞、恶病质和贫血。IL-6 与肺癌对表皮生长因子抑制剂的耐药性有关。针对 IL-6 的单克隆抗体治疗可能是治疗肺癌炎症微环境的有效方法。
了解肺癌中涉及的炎症途径，包括 IL-6 的核心作用，以及炎症如何影响肺癌的病程和治疗。靶向 IL-6 的 mAb ALD518 及其在晚期 NSCLC 中的研发和应用。ALD518 的临床前和 I 期和 II 期研究，重点是 NSCLC。ALD518 将来如何用于 NSCLC。
IL-6 介导的炎症可能导致 NSCLC 相关发病率和死亡率。在临床前和 I 期和 II 期试验中，靶向 IL-6 的 ALD518 似乎耐受性良好，并改善了 NSCLC 相关的贫血和恶病质。其他临床结果需要进一步研究，可能包括对总生存期、与肺癌相关的高凝状态和对表皮生长因子途径抑制剂耐药性降低的影响。
