Lipid Signaling Pathways in Cancer

描述(由申请者提供)：本申请寻求支持两年一度的科学会议系列，题为“癌症中的脂质信号通路”。这些会议由美国实验生物学学会联合会(FASE B)赞助，是其两年一度的夏季研究会议(SRC)系列的一部分，并由梅奥临床医学院的艾伦·P·菲尔兹博士和宾夕法尼亚大学医学院的马塞洛·卡赞涅茨博士共同组织。下一次会议将于2009年7月19日至24日在亚利桑那州无忧无虑的无忧无虑度假村举行，随后的会议计划在2011年夏天和2013年夏天举行。通过资助这一申请提供的支助将部分用于支付初级研究人员的注册费和旅费，包括应邀在这些会议上介绍他们的工作的研究生和博士后研究员。这次会议为期4天，邀请了30多位该领域的领导人出席，介绍了这一高度相关的癌症研究领域的最新突破。在脂质信号领域的最新令人兴奋的进展将被提出，这些进展强化了脂质介体在癌症的发生和发展中发挥关键作用的概念。例如，在许多人类癌症中发现了参与磷脂酰肌醇和PKC信号转导的蛋白质的肿瘤特异性基因改变，突显了这些脂质信号转导途径在肿瘤发生中的重要性。PI3-K/Akt/mTOR，PKC，DAG依赖的GTP酶，RAS家族GTP酶的脂质修饰，以及鞘磷脂酶信号转导等令人兴奋的发现也将被讨论，以及这些途径在肿瘤发生中的作用。这些脂质信号通路中的许多都是开发新的癌症治疗策略的有吸引力的候选者。事实上，针对其中几个脂质信号通路的新疗法目前正在临床上进行评估。因此，将特别强调对脂类信号通路的翻译研究，这可能会导致有希望的新的临床癌症治疗。鉴于这一肥沃研究领域的快速发展，两年一次的会议时间表是适当的。没有其他定期安排的会议聚焦于这一新兴领域，这一系列会议将成为有效科学交流的主要论坛，这将有助于在未来五年推动这一领域的进展。 与公共健康相关：脂质信号通路的功能允许细胞与环境进行交流并对其做出反应，进而发挥适当的作用。在人类癌症中，这些脂质信号机制经常被失调，要么是由于遗传或体细胞基因突变，要么是由于编码脂质信号通路关键成分的基因的表达或活性的表观遗传变化。这个项目的一个主要焦点是提供一个论坛，讨论脂质信号机制的基本知识的进展，以及这些知识如何转化为将影响临床肿瘤学实践的新的治疗策略。

DESCRIPTION (provided by applicant): This application seeks support for a biennial scientific conference series entitled 'Lipid Signaling Pathways in Cancer'. The conferences are sponsored by the Federation of the American Societies for Experimental Biology (FASEB) as part of their biennial Summer Research Conference (SRC) Series and are co- organized by Dr. Alan P. Fields of the Mayo Clinic College of Medicine and Dr. Marcelo Kazanietz of the University of Pennsylvania School of Medicine. The next conference will be held at the Carefree Resort in Carefree, Arizona on July 19-24, 2009 with subsequent conferences scheduled for summer of 2011 and summer 2013. Support provided through funding of this application will be used to partially finance the costs of registration fees and travel expenses for junior investigators, including graduate students and post-doctoral fellows, invited to present their work at these conferences. The conference is held over the course of 4 days, with more than 30 invited leaders in the field attending to present the latest breakthroughs in this highly relevant area of cancer research. Recent exciting developments in the field of lipid signaling will be presented that have reinforced the concept that lipid mediators play key roles in the initiation and progression of cancer. For example, tumor-specific genetic alterations in proteins involved in phosphoinositide and PKC signaling have been found in many human cancers, highlighted the importance of these lipid signaling pathways in tumorigenesis. Exciting findings in PI 3-K/Akt/mTOR, PKC, DAG-dependent GTPases, lipid modifications of Ras family GTPases, and sphingomyelinase signaling and the role of these pathways in tumorigenesis will also be discussed. Many of these lipid signaling pathways are attractive candidates for development of novel therapeutic strategies for cancer treatment. Indeed, novel therapeutics that target several of these lipid signaling pathways are currently being evaluated in the clinic. Particular emphasis will therefore be placed on translational studies of lipid signaling pathways that may lead to promising new clinical cancer treatments. Given the rapid developments in this fertile research area, a biennial meeting schedule is appropriate. No other regularly scheduled conference focuses on this burgeoning area, and this conference series is poised to become a major forum for effective scientific interchange that will serve to facilitate advances in this field over the next five years. Public Health Relevance: Lipid signaling pathways function to allow cells to communicate with and respond to their environment, and in turn to function appropriately. In human cancer, these lipid signaling mechanisms are often dysregulated, either by inherited or somatic genetic mutations, or as a result of epigenetic changes in expression or activity of the genes encoding key components of lipid signaling pathways. A major focus of this project is to provide a forum to discuss advances in basic knowledge of lipid signaling mechanisms and how this knowledge is being translated into novel therapeutic strategies that will impact clinical oncology practice.