Carbone Michele, Yang Haining
Thoracic Oncology, University of Hawaii Cancer Center, Honolulu, HI 96816, USA.
Ann Transl Med. 2017 Jun;5(11):238. doi: 10.21037/atm.2017.04.29.
Recent discoveries have elucidated some of the mechanisms responsible for the development of mesothelioma. These discoveries are: (I) the critical role of chronic inflammation in promoting mesothelioma growth, driven by the release of high mobility group box protein-1 (HMGB1) following asbestos deposition in tissues and its potential role as a biomarker to identify asbestos exposed individuals and mesothelioma patients; (II) the discovery that inherited heterozygous germline mutations of the deubiquitylase BRCA-associated protein 1 () cause a high incidence of mesothelioma in some families; and that (III) germline BAP1 mutations lower the threshold of asbestos required to cause mesothelioma in mice, evidence of gene X environment interaction. These findings together with the identification of novel serum biomarkers, including HMGB1, Fibulin-3, etc., promise to revolutionize screening and treatment of this malignancy in the coming years.
最近的发现阐明了一些导致间皮瘤发生的机制。这些发现包括：（I）慢性炎症在促进间皮瘤生长中的关键作用，这是由组织中石棉沉积后高迁移率族蛋白B1（HMGB1）的释放所驱动的，并且其作为生物标志物在识别石棉暴露个体和间皮瘤患者方面具有潜在作用；（II）发现去泛素化酶BRCA相关蛋白1（BAP1）的遗传性杂合种系突变在一些家族中导致间皮瘤的高发病率；以及（III）种系BAP1突变降低了小鼠发生间皮瘤所需的石棉阈值，这是基因与环境相互作用的证据。这些发现连同新型血清生物标志物（包括HMGB1、纤维连接蛋白-3等）的鉴定，有望在未来几年彻底改变这种恶性肿瘤的筛查和治疗方式。
