Signal Transduction Research Program

项目SuIVIMARY(请参阅说明)： 信号转导(ST)研究计划促进旨在了解癌症发生和癌症进展中的信号转导途径的研究。从长远来看，这将有助于开发有效的癌症治疗方法，并将靶向药物与个别患者进行最佳匹配，以实现最大的治疗效果。信号转导研究计划是在本CCSG的上一个周期中基于两个主要前提建立的。首先，大多数人类癌症是由细胞通路的失调驱动的，这些通路通常将激素依赖的信号与与癌症相关的基本细胞过程联系起来，包括调节细胞分裂、保护细胞免受凋亡、肿瘤血管生成、谱系限制以及与癌症进展相关的变化。其次，信号转导分子，包括肽生长因子、受体激酶、非受体激酶及其调节的通路组件，已成为新癌症治疗的重要靶点。攻击致癌信号产品及其辅助途径的有效癌症新疗法组合已扩大到包括数十种美国FDA批准的药物，还有更多药物正在临床开发管道中。当这些药物用于基于遗传或功能标准的患者选择时，会产生很大的影响，但到目前为止只适用于少数癌症患者。此外，随着临床经验的增加，出现了一个重大的实际问题：对这些药物的耐药性迅速发展，即使是在最初反应剧烈的患者中也是如此。因此，科技研究计划的一个重要新的研究领域是耐药机制，以及预测和战胜耐药的手段。 31名ST项目成员来自耶鲁学院和耶鲁医学院的14个系。他们包括研究与癌症相关的信号转导研究的方方面面的教职员工，包括受体信号转导机制、信号通路、细胞骨架、细胞极性、细胞内蛋白质运输和整合信号网络的工作。以癌症生物学为中心的研究项目招聘了六名新教师，增加了对癌症的关注。自上一个CCSG周期以来，ST计划成员已经发表了412篇(2006-2012年)癌症相关论文，其中24篇(6%)是规划内的，105篇(25%)是规划间的。ST计划的癌症研究资金总额为每年670万美元(总成本1040万美元，其中840万美元由同行评审，370万美元由NCI资助)。

PROJECT SUIVIMARY (See instructions): The Signal Transduction (ST) Research Program promotes studies aimed at understanding of signal transduction pathways in carcinogenesis and cancer progression. In the long run, this will facilitate development of effective cancer therapeutics and optimal matching of targeted drugs to individual patients for maximal therapeutic impact The Signal Transduction Research Program was established in the previous cycle of this CCSG based on two major premises. First, the majority of human cancers are driven by dysregulation of cellular pathways that normally link hormone-dependent signaling to fundamental cellular processes relevant to cancer including regulation of cell division, protection from apoptosis, tumor angiogenesis, lineage restrictions, and changes associated with cancer progression. Second, signal transduction molecules, including peptide growth factors, receptor kinases, non-receptor kinases, and components of pathways that they regulate, have emerged as important targets for new cancer therapies. The portfolio of effective new cancer therapies that attack oncogenic signaling products and their subservient pathways has expanded to encompass dozens of US FDA-approved pharmaceuticals, with many more in the clinical developmental pipeline. These drugs, when, employed with patient selection based on genetic or functional criteria, have great impact, but as yet are only appropriate for a minority of cancer patients. Moreover, with increased experience in the clinic, a major practical issue has emerged: the rapid development of resistance to these agents, even in patients who initially responded dramatically. Hence, an important new area of investigation in the ST Research Program is the mechanisms of drug resistance, and the means to anticipate and defeat them. The 31 ST program members are drawn from 14 departments at Yale College and Yale Medical School. They include faculty investigating all aspects of signal transduction research related to cancer, including work on receptor signaling mechanisms, signaling pathways, cytoskeleton, cell polarity, intracellular protein trafficking, and integrated signaling networks. Recruitment of six new faculty with research programs centered on cancer biology has increased cancer focus. Since the last CCSG cycle, ST program members have published 412 (2006-2012) cancer related papers, of which 24 (6%) were intra-programmatic and 105 (25%) inter-programmatic. The total cancer research funding of the ST Program is $6.7M annual direct costs ($10.4M total costs, of which $8.4M is peer-reviewed, and $3.7 M NCI-funded).