Lipid Signaling Pathways in Cancer

描述（由申请人提供）：本申请寻求对题为“癌症中的脂质信号通路”的两年期科学会议系列的支持。这些会议由美国实验生物学学会联合会（FASEB）赞助，作为其两年一度的夏季研究会议（SRC）系列的一部分，并由马约临床医学院的Alan P. Fields博士和宾夕法尼亚大学医学院的Marcelo Kazanietz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，随后的会议定于2011年夏季和2013年夏季举行。通过资助这一申请提供的支助将用于部分资助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其工作的研究生和博士后研究员。该会议为期4天，邀请了30多位该领域的领导人出席，介绍这一高度相关的癌症研究领域的最新突破。脂质信号传导领域的最新令人兴奋的发展将被提出，这加强了脂质介质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酸肌醇和PKC信号传导的蛋白质中的肿瘤特异性遗传改变，突出了这些脂质信号传导途径在肿瘤发生中的重要性。PI 3-K/Akt/mTOR，PKC，DAG依赖性GTP酶，Ras家族GTP酶的脂质修饰和鞘磷脂酶信号传导以及这些途径在肿瘤发生中的作用也将被讨论。这些脂质信号通路中的许多是用于开发癌症治疗的新治疗策略的有吸引力的候选者。事实上，靶向这些脂质信号通路中的几种的新疗法目前正在临床上进行评估。因此，将特别强调脂质信号通路的翻译研究，这可能导致有前途的新的临床癌症治疗。鉴于这一丰富的研究领域的迅速发展，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专注于这一新兴领域，这一系列会议将成为有效科学交流的主要论坛，有助于在未来五年内促进这一领域的进步。 公共卫生相关性：脂质信号通路的功能是允许细胞与其环境沟通并对其环境做出反应，从而适当地发挥作用。在人类癌症中，这些脂质信号传导机制通常失调，或者是由于遗传或体细胞遗传突变，或者是由于编码脂质信号传导途径关键组分的基因的表达或活性的表观遗传变化。该项目的一个主要重点是提供一个论坛，讨论脂质信号传导机制的基础知识的进展，以及这些知识如何转化为新的治疗策略，将影响临床肿瘤学实践。

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.