Molecular Pathways: Blockade of the PRLR Signaling Pathway as a Novel Antihormonal Approach for the Treatment of Breast and Prostate Cancer
Molecular Pathways: Blockade of the PRLR Signaling Pathway as a Novel Antihormonal Approach for the Treatment of Breast and Prostate Cancer
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DOI：
10.1158/1078-0432.ccr-12-0138
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发表时间：
2013-04-01
影响因子：
11.5
通讯作者：
Wasserman, Ernesto
中科院分区：
文献类型：
--
作者：
Damiano, Jason S.;Wasserman, Ernesto
催乳素（PRL）-催乳素受体（PRLR）信号复合物与乳腺癌和前列腺癌的病理学有关。在乳腺和前列腺上皮细胞中，许多促癌细胞内信号传导途径被PRL激活，导致许多模型系统中细胞增殖、存活和肿瘤发生增强。新出现的证据表明，靶向人类癌症中的PRL-PRLR轴可能代表了一种未开发的治疗干预途径，并且鉴于PRLR和其他信号转导途径之间的广泛串扰，这是一种潜在的手段，通过这种手段，其他抗癌药物可以在临床上变得更有效。LFA 102是一种有效的抗PRLR中和抗体，可有效消除该受体在体内的功能，在临床前模型中介导显著的抗肿瘤作用。该抗体在动物中的清洁安全性特征和迄今为止的临床经验表明，阻断人类肿瘤中的PRLR信号通路可能几乎没有显著的毒理学后果，并且可能是治疗癌症的有希望的方法。一项针对乳腺癌和前列腺癌患者的I期试验正在进行中，以更好地了解LFA 102的临床效用以及PRL对人类癌症维持和进展的贡献。临床癌症研究; 19（7）;1644-50。(C)2013年AACR。
The prolactin (PRL)-prolactin receptor (PRLR) signaling complex has been implicated in the pathology of breast and prostate carcinoma. A multitude of pro-oncogenic intracellular signaling pathways are activated by PRL in breast and prostate epithelial cells, leading to enhanced cellular proliferation, survival, and tumorigenesis in numerous model systems. Emerging evidence suggests that targeting the PRL-PRLR axis in human cancer may represent an unexploited avenue for therapeutic intervention and, given the extensive cross-talk between PRLR and other signal transduction pathways, a potential means through which other anticancer agents could be rendered more efficacious in the clinic. LFA102 is a potent anti-PRLR neutralizing antibody that efficiently abrogates the function of this receptor in vivo, mediating significant antitumor effects in preclinical models. The clean safety profile of this antibody in animals and in the clinical experiences to date suggests that blocking the PRLR signaling pathway in human tumors may have few significant toxicologic consequences and may be a promising approach to treating cancer. A phase I trial in patients with breast and prostate cancer is underway to better understand the clinical utility of LFA102 and the contribution of PRL to the maintenance and progression of human cancer. Clin Cancer Res; 19(7);1644-50. (C) 2013 AACR.