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研究表明,不仅内分泌而且自分泌/旁分泌产生的催乳素(prolactin,PRL)在体外细胞水平、体内多种转基因和基因敲除动物模型以及一定数量的人群流行病学调查水平上,均与乳腺肿瘤的发病机制和病程进展有关。由于传统多巴胺类似物在乳腺肿瘤治疗过程中不能有效抑制垂体外PRL的产生,因此并不能有效抑制乳腺肿瘤的生长。为此,研究者设计了多种催乳素受体(prolactin receptor,PRLR)拮抗剂,包括内分泌PRL抑制剂、链突变拮抗剂、链嵌合体、PRL诱导的信号通路抑制剂等。链突变拮抗剂通过向天然PRL多肽链引入不同的突变来竞争性抑制内源性PRL与PRLR结合,是目前研究较多的一类PRLR拮抗剂。文中主要介绍链突变PRLR拮抗剂的发展、性质、作用机制以及在乳腺癌临床治疗中的应用前景。
Studies have shown that not only endocrine but also autocrine / paracrine prolactin (PRL) are associated with breast cancer in vitro at cellular level, in vivo transgenic and knockout animal models, and in a population-based epidemiological survey The pathogenesis of cancer and the progress of the disease. Traditional dopamine analogues can not effectively inhibit the growth of breast tumors because they can not effectively inhibit the production of pituitary PRL during the treatment of breast tumors. To this end, the researchers designed a variety of prolactin receptor (PRLR) antagonists, including endocrine PRL inhibitors, chain mutation antagonists, chimeras, PRL-induced signal pathway inhibitors. Chain Mutant Antagonists competitively inhibit the binding of endogenous PRL to PRLR by introducing different mutations into the native PRL polypeptide chain, and are currently a well-studied class of PRLR antagonists. This article mainly introduces the development, properties, mechanism of action of chain-mutation PRLR antagonists and its application prospects in the clinical treatment of breast cancer.