Conference on Hormonal Regulation of Tumorigenesis

描述（由申请人提供）：类固醇激素是乳腺和前列腺肿瘤生长的关键因素。类固醇的作用由类固醇激素受体介导，类固醇激素受体是配体激活转录因子的核受体家族的成员。受体活性的类型和大小取决于细胞中的共激活因子、共抑制因子和细胞信号传导途径的活性;这些因子及其与受体的相互作用是潜在的治疗靶点。激素消融和/或抗激素疗法通常用于治疗癌症。然而，肿瘤对这些治疗产生了抗药性。 尽管最初假设耐药肿瘤绕过了对类固醇受体的要求，但令人兴奋的新数据表明这些肿瘤仍然是受体依赖性的，并且受体表达、辅调节因子表达和/或细胞信号传导的改变允许受体在缺乏生理水平的雄激素或雌激素的情况下继续发挥作用。因此，类固醇受体在肿瘤中的作用比最初认识到的要大，并提出了一系列关于如何阻断受体活性的新问题。在过去几年中，至少有四个与该主题相关的RFA支持肿瘤中受体作用的问题，并计划在2004年举办两次有限的NIH研讨会，讨论这些问题的部分内容。类固醇对乳腺和前列腺的作用有许多相似之处。该计划是独一无二的，它提供了一个机会来比较两种肿瘤的作用，目的是为治疗提供新的机会。将具有受体及其调控途径专业知识的研究人员与研究乳腺癌和前列腺癌的人员聚集在一起，对于促进这一领域的进展非常重要。重要的是，它将有助于向对这一领域感兴趣的研究生和博士后研究员介绍这一高度优先领域的主要问题，并让他们有机会展示自己的工作，并与该领域的领导人进行讨论。

DESCRIPTION (provided by applicant): Steroid hormones are key factors in breast and prostate tumor growth. The actions of the steroids are mediated by steroid hormone receptors, members of the nuclear receptor family of ligand-activated transcription factors. The types and magnitude of the activities of the receptors are dependent upon the cohort of coactivators, corepressors, and activity of cell signaling pathways in the cell; these factors and their interaction with receptors are potential therapeutic targets. Hormone ablation and/or anti-hormone therapies are commonly used to treat the cancers. However, tumors become resistant to these treatments. Although it was initially assumed that the resistant tumors had bypassed the requirements for the steroid receptors, there is exciting new data indicating that these tumors remain receptor-dependent and that alterations in receptor expression, coregulator expression and/or cell signaling permit the receptors to continue to function in the absence of physiological levels of androgens or estrogens. Consequently, the contribution of steroid receptor action in hormonally regulated tumors is greater than initially realized and raises a new set of questions regarding how to block the receptor activity. That the question of receptor actions in tumors is currently of high priority is supported by at least four RFAs related to this topic in the last few years and plans for two limited NIH workshops in 2004 addressing portions of these questions. There are many parallels between steroid action in breast and prostate. This program is unique in providing an opportunity to compare the actions in the two tumors with the goal of providing new opportunities for therapies. Bringing together investigators with expertise in receptors and their regulatory pathways with those who study breast and prostate cancer is important in facilitating progress in this area. Importantly, it will aid in introducing graduate students and post-doctoral fellows interested in this area to the major questions in this high priority field as well as giving them an opportunity to present there own work and to discuss it with leaders in the field.