科学家或开发出治疗胰腺癌的潜在靶向药物

  胰腺癌是一种致死性癌症且患者预后较差，同时这种癌症也是美国四大致命性癌症中的一种；胰腺癌在早期阶段很难被诊断出来，而且扩散非常迅速，目前几乎没有有效的治疗方法。近日一项刊登在国际杂志Nature Reviews Cancer上的研究论文中，来自休斯顿大学的研究人员通过研究开发了一种药物或可帮助改善胰腺癌患者的生存，甚至可以帮助有效清除癌细胞。
  研究者Chin-Yo Lin教授说道，我们发现了肝脏X受体（LXRs）的重要角色，其或许可以作为治疗胰腺癌的新型靶点帮助开发新型疗法；文章中研究者检测了患者肿瘤样本中LXRs的水平，并且研究了候选药物对培养中的胰腺癌细胞的LXRs受体的靶向作用效应。LXRs是胆固醇、葡萄糖代谢及炎性反应调节的重要调节子，目前研究者有足够证据显示LXRs可以参与多种癌症的恶化过程。
  后期研究者将确定是否LXRs在所有肿瘤或者部分对靶向LXRs药物敏感的特殊肿瘤中进行表达，另一个研究目的就是检测靶向药物对鼠类动物模型机体的胰腺癌的作用效果，基于目前的研究数据，研究者计划后期开发更好的药物来靶向作用胰腺癌中的LXRs。如今研究者已经在病人肿瘤样本中进行了一些和LXR表达相关的初步研究，而且他们还计划分析更多的样本，而近来又有研究表明靶向作用LXRs的化合物或可有效减缓鼠类模型机体中来自人类机体移植的胰腺肿瘤。
  Lin说道，我们研究发现了一系列可以被药物靶向作用的受体，我们希望这可以促进我们对转化医学领域的研究，后期我们还将进行更多深入研究来开发更多候选药物以及进行更多的人类机体临床测试。下一步研究者将手机来自更多病人样本的信息以及临床前的研究数据，基于目前的研究研究人员将利用当前的化合物或技术能力开展更多的胰腺癌疗法临床研究。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Targeting liver X receptors in cancer therapeutics
Nature Reviews Cancer      doi:10.1038/nrc3912
Chin-Yo Lin & Jan-Åke Gustafsson
Members of the nuclear receptor superfamily of ligand-dependent transcription factors carry out vital cellular functions and are highly druggable therapeutic targets. Liver X receptors (LXRs) are nuclear receptor family members that function in cholesterol transport, glucose metabolism and the modulation of inflammatory responses. There is now accumulating evidence to support the involvement of LXRs in a variety of malignancies and the potential efficacy of their ligands in these diseases. This Review summarizes the discovery and characterization of LXRs and their ligands, their effects and mechanisms in preclinical cancer models, and the future directions of basic and translational LXR research in cancer therapeutics.

Antiproliferative Effects and Mechanisms of Liver X Receptor Ligands in Pancreatic Ductal Adenocarcinoma Cells
PLoS ONE   DOI: 10.1371/journal.pone.0106289
Nicholes R. Candelaria , Sridevi Addanki , Jine Zheng, Trang Nguyen-Vu, Husna Karaboga, Prasenjit Dey, Chiara Gabbi, Lise-Lotte Vedin, Ka Liu, Wanfu Wu, Philip K. Jonsson, Jean Z. Lin, Fei Su, Lakshmi Reddy Bollu, Sally E. Hodges, Amy L. McElhany, Mehdi A. Issazadeh, William E. Fisher, Michael M. Ittmann, Knut R. Steffensen, Jan-Åke Gustafsson, Chin-Yo Lin
Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect early and is often resistant to standard chemotherapeutic options, contributing to extremely poor disease outcomes. Members of the nuclear receptor superfamily carry out essential biological functions such as hormone signaling and are successfully targeted in the treatment of endocrine-related malignancies. Liver X receptors (LXRs) are nuclear receptors that regulate cholesterol homeostasis, lipid metabolism, and inflammation, and LXR agonists have been developed to regulate LXR function in these processes. Intriguingly, these compounds also exhibit antiproliferative activity in diverse types of cancer cells. In this study, LXR agonist treatments disrupted proliferation, cell-cycle progression, and colony-formation of PDAC cells. At the molecular level, treatments downregulated expression of proteins involved in cell cycle progression and growth factor signaling. Microarray experiments further revealed changes in expression profiles of multiple gene networks involved in biological processes and pathways essential for cell growth and proliferation following LXR activation. These results establish the antiproliferative effects of LXR agonists and potential mechanisms of action in PDAC cells and provide evidence for their potential application in the prevention and treatment of PDAC.