Section of Airways Disease, National Heart and Lung Institute, Imperial College London, London, UK.
Ther Adv Respir Dis. 2010 Feb;4(1):19-34. doi: 10.1177/1753465809352792. Epub 2010 Jan 5.
Respiratory diseases such as chronic obstructive pulmonary disease [COPD], severe asthma, cystic fibrosis [CF] and idiopathic pulmonary fibrosis [IPF] are inadequately controlled by current therapies. The underlying molecular mechanisms and pathogenesis of these diseases remain unclear, making identification and validation of potential new therapeutic targets difficult. However, recent studies have identified the central signalling mediator PI3K as playing an integral role in the immune system including initiation and maintenance of inflammatory responses. Specifically, the relatively leukocyte-specific PI3Kgamma and PI3Kdelta isoforms are central to leukocyte function and can be targeted pharmacologically. Early to man studies using selective PI3K isoform inhibitors are required to determine whether they have a future in treating respiratory disease, particularly in controlling both innate and adaptive inflammatory responses as well as restoring glucocorticoid function and reducing tumorigenesis.
当前的治疗方法无法充分控制慢性阻塞性肺疾病（COPD）、严重哮喘、囊性纤维化（CF）和特发性肺纤维化（IPF）等呼吸道疾病。这些疾病的潜在分子机制和发病机制尚不清楚，这使得确定和验证潜在的新治疗靶点变得困难。然而，最近的研究已经确定中央信号介质 PI3K 在免疫系统中发挥着重要作用，包括炎症反应的启动和维持。具体而言，相对白细胞特异性的 PI3Kgamma 和 PI3Kdelta 同工型对于白细胞功能至关重要，并且可以通过药理学方法进行靶向治疗。需要进行早期人体研究，以确定选择性 PI3K 同工型抑制剂是否具有治疗呼吸道疾病的未来，特别是在控制先天和适应性炎症反应以及恢复糖皮质激素功能和减少肿瘤发生方面。
