Goyeneche Alicia A, Telleria Carlos M
Division of Basic Biomedical SciencesSanford School of Medicine, The University of South Dakota, Vermillion, South Dakota 57069, USA.
Division of Basic Biomedical SciencesSanford School of Medicine, The University of South Dakota, Vermillion, South Dakota 57069, USA
Reproduction. 2015 Jan;149(1):R15-33. doi: 10.1530/REP-14-0416. Epub 2014 Sep 24.
Antiprogestins constitute a group of compounds, developed since the early 1980s, that bind progesterone receptors with different affinities. The first clinical uses for antiprogestins were in reproductive medicine, e.g., menstrual regulation, emergency contraception, and termination of early pregnancies. These initial applications, however, belied the capacity for these compounds to interfere with cell growth. Within the context of gynecological diseases, antiprogestins can block the growth of and kill gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix. They can also interrupt the excessive growth of cells giving rise to benign gynecological diseases such as endometriosis and leiomyomata (uterine fibroids). In this article, we present a review of the literature providing support for the antigrowth activity that antiprogestins impose on cells in various gynecological diseases. We also provide a summary of the cellular and molecular mechanisms reported for these compounds that lead to cell growth inhibition and death. The preclinical knowledge gained during the past few years provides robust evidence to encourage the use of antiprogestins in order to alleviate the burden of gynecological diseases, either as monotherapies or as adjuvants of other therapies with the perspective of allowing for long-term treatments with tolerable side effects. The key to the clinical success of antiprogestins in this field probably lies in selecting those patients who will benefit from this therapy. This can be achieved by defining the genetic makeup required - within each particular gynecological disease - for attaining an objective response to antiprogestin-driven growth inhibition therapy.Free Spanish abstractA Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/1/15/suppl/DC1.
抗孕激素是自20世纪80年代初开始研发的一类化合物,它们以不同的亲和力与孕激素受体结合。抗孕激素最初在生殖医学中的临床应用包括月经调节、紧急避孕和早期妊娠终止。然而,这些最初的应用掩盖了这些化合物干扰细胞生长的能力。在妇科疾病的背景下,抗孕激素可以阻止妇科相关癌细胞的生长并杀死这些细胞,例如起源于乳腺、卵巢、子宫内膜和宫颈的癌细胞。它们还可以阻止导致诸如子宫内膜异位症和平滑肌瘤(子宫肌瘤)等良性妇科疾病的细胞过度生长。在本文中,我们对文献进行了综述,这些文献支持抗孕激素对各种妇科疾病细胞的抗生长活性。我们还总结了已报道的这些化合物导致细胞生长抑制和死亡的细胞和分子机制。过去几年获得的临床前知识提供了有力证据,鼓励使用抗孕激素来减轻妇科疾病的负担,无论是作为单一疗法还是作为其他疗法的辅助药物,以期实现具有可耐受副作用的长期治疗。抗孕激素在该领域临床成功的关键可能在于选择那些将从这种治疗中受益的患者。这可以通过确定在每种特定妇科疾病中实现对抗孕激素驱动的生长抑制治疗的客观反应所需的基因组成来实现。免费西班牙文摘要本摘要的西班牙文翻译可在http://www.reproduction-online.org/content/149/1/15/suppl/DC1免费获取。