Reply: hormonally targeted therapy for women with lymphangioleiomyomatosis.
Reply: hormonally targeted therapy for women with lymphangioleiomyomatosis.
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答复：针对女性淋巴管平滑肌瘤病的激素靶向治疗。
DOI：
10.1165/rcmb.2013-0324le
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发表时间：
2014
影响因子：
6.4
通讯作者：
Yu,Jane
中科院分区：
文献类型：
--
作者：
Yu,Jane
We read with interest the article by Li and colleagues, which demonstrated that Faslodex (fulvestrant) promotes blockade of the dissemination of lymphangioleiomyomatosis (LAM) cells through antagonism on estradiol receptors in mice (1). This study reinforces our belief that hormonal blockade has a potential role in the treatment of patients with LAM, which could be explained by its preferential occurrence in women of reproductive age and the presence of hormonal receptors in LAM cells. Although previous studies that have evaluated antihormonal therapy in LAM produced controversial results, including one from our group, randomized trials that could lead to robust conclusions have not been performed (2–4). An important finding of this study was that Faslodex has blocked expression and activity of matrix metalloproteinase (MMP)-2, which is involved in lung metastasis and in cystic destruction of the lungs in LAM. We suggest that the association of doxycycline, an effective MMP inhibitor with a safety profile, to Faslodex may enhance the blockade of MMP activity, which could contribute to the reduction of cystic formation (1, 5). Randomized trials are necessary to establish the role of hormonal blockade on the progression of LAM because estradiol is an important pathway involved in its pathophysiology, and also there is currently no definitive treatment for this disease. There is also a favorable perspective with Faslodex because its mechanism of action is different from other hormonal treatments, which is to promote the direct blockade of the estrogen receptors. More recently, the results of the MILES trial showed that sirolimus, an inhibitor of the mammalian target of rapamycin and a promising drug for LAM, stabilized lung function and improved functional performance and quality of life only during the treatment period (6). As different pathways are involved in the proliferation of LAM cells, it would be important to test a combination of therapies that could increase the durability of the clinical and functional responses that are observed in a proportion of patients that use these drugs in isolated regimens. In the near future, we hope to participate in clinical trials evaluating the impact of the association of treatment modalities, such as hormonal blockade, doxycycline, and sirolimus, acting on different pathways involved in the pathogenesis of LAM in a similar way to the therapeutic strategy used in malignant tumors (1–6).■
