Song Xixi, Cai Hui, Yang Chengyu, Xue Xiaomin, Wang Jian, Mo Yuqing, Zhu Mengchan, Zhu Guiping, Ye Ling, Jin Meiling
Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Med (Lausanne). 2020 Sep 24;7:554134. doi: 10.3389/fmed.2020.554134. eCollection 2020.
Lymphangioleiomyomatosis (LAM) is a rare systemic neoplastic disease that exclusively happens in women. Studies focusing on LAM and tuberous sclerosis complex (TSC) have made great progress in understanding the pathogenesis and searching for treatment. The inactive mutation of TSC1 or TSC2 is found in patients with LAM to activate the crucial mammalian target of rapamycin (mTOR) signaling pathway and result in enhanced cell proliferation and migration. However, it does not explain every step of tumorigenesis in LAM. Because cessation of rapamycin would break the stabilization of lung function or improved quality of life and lead to disease recurrent, continued studies on the pathogenesis of LAM are necessary to identify novel targets and new treatment. Researchers have found several aberrant regulations that affect the mTOR pathway such as its upstream or downstream molecules and compensatory pathways in LAM. Some therapeutic targets have been under study in clinical trials. New methods like genome-wide association studies have located a novel gene related to LAM. Herein, we review the current knowledge regarding pathogenesis and treatment of LAM and summarize novel targets of therapeutic potential recently.
淋巴管平滑肌瘤病（LAM）是一种仅发生于女性的罕见全身性肿瘤疾病。针对LAM和结节性硬化症（TSC）的研究在理解发病机制和寻找治疗方法方面取得了很大进展。在LAM患者中发现TSC1或TSC2的失活突变会激活关键的雷帕霉素靶蛋白（mTOR）信号通路，导致细胞增殖和迁移增强。然而，这并不能解释LAM肿瘤发生的每一个步骤。由于停用雷帕霉素会破坏肺功能的稳定或降低生活质量，并导致疾病复发，因此有必要继续研究LAM的发病机制，以确定新的靶点和新的治疗方法。研究人员已经发现了一些影响mTOR通路的异常调节，如LAM中其上游或下游分子以及代偿途径。一些治疗靶点正在临床试验中进行研究。全基因组关联研究等新方法已经定位了一个与LAM相关的新基因。在此，我们综述了目前关于LAM发病机制和治疗的知识，并总结了近期具有治疗潜力的新靶点。
