Cold Spring Harbor Laboratory Cancer Research Center

描述(由申请人提供)：该计划应用了生物化学、细胞生物学、遗传学和人类癌症的小鼠模型的组合，统一的目标是揭示关键的肿瘤发生途径。靶向治疗的成功继续强化了这样一种观点，即了解癌细胞的生物学是治疗这种疾病的关键。在其35年的历史中，该计划一直专注于将DNA肿瘤病毒的经验转化为对正常细胞和肿瘤生物学的理解。这仍然是该计划的重点；然而，随着观点从病毒转移到细胞蛋白质，重点也从癌细胞演变到将肿瘤作为组织的更广泛的考虑。该方案由六个高度整合和相互支持的项目和四个核心组成。该计划是统一的购买几个主题，贯穿其组成部分。首先，人们确信，DNA肿瘤病毒是由进化驱动的，目标是掌握肿瘤生长关键的最小一组基本细胞网络。通过从病毒蛋白本身向下游转移到与其最接近的细胞对应物，该计划中的项目可能会努力了解c-Myc的变化如何促进不同细胞和组织环境中的转化。该计划还统一了对一类新的RNA调节分子--作为癌基因的microRNAs--的研究。该计划还利用这些作为研究基因功能的实验工具。最后，该计划是在复杂的癌症模型的背景下进行的，这些模型使用工程干细胞和祖细胞来快速重建器官系统，几乎可以进行任何所需的基因改变。该计划的发现有可能为当前疗法的有效应用提供信息，并识别可能成为新治疗剂开发目标的蛋白质和网络。

DESCRIPTION (provided by applicant): The Program applies a combination of biochemistry, cell biology, genetics and mouse models of human cancer with a unified goal of revealing key tumorigenic pathways. The success of targeted therapeutics continues to reinforce the view that understanding the biology of the cancer cell is the key to treating this disease. Throughout its 35 year history, this Program has focused on translating lessons from DNA tumor viruses into an understanding of both normal cellular and tumor biology. This remains a focus of the Program; however, as the view has shifted from viral to cellular proteins, so is the emphasis evolving from the cancer cell to a broader consideration of the tumor as a tissue. This Program is composed of six highly integrated and mutually supporting Projects and four Cores. The Program is unified buy several themes which run throughout its components. First is the conviction that DNA tumor viruses have been driven by evolution to target the minimal set of fundamental cellular networks that hold the keys to tumorigenic growth. By moving downstream from the viral proteins themselves to their closest cellular counterparts, may projects within the program strive to understand how alterations in c-Myc promote transformation in different cellular and tissue contexts. The Program is also unified in the study of a new class of RNA regulatory molecules, the microRNAs, that act as oncogenes. The Program also exploits these as experimental tools to study gene function. Finally, the Program is cast in the context of sophisticated cancer models that use engineered stem and progenitor cells to rapidly reconstitute organ systems with nearly any desired genetic alteration. The findings from this Program have the potential both to inform the effective application of current therapies and to identify proteins and networks that may become targets for the development of new therapeutic agents.