Program Project in Models of Breast Cancer

描述(由申请人提供)：建议是一个在乳腺癌动物和实验室模型方面的生产性、综合性、创新性项目的继续，具有实际和预期的临床可译性。其目的是解决基本的生物学问题，以提高我们对转移和异常生长调节的了解，从而改善乳腺癌预测、治疗效益和治疗的方方面面。它由四个项目组成，每个项目由该领域的一名领导者领导，一个提供监督和管理的管理核心，以及一个高度创新的RNAi核心，提供关键试剂和转基因小鼠模型。避免重复劳动、智力和物质的协同以及面向真正的临床需求是其特点 这一努力的结果。这些项目及其主要研究人员是：(1)转化生长因子-β、PI3K和HER2通路在乳腺癌转移中的作用(Joan Massague，Ph.D.)，(2)Id1在乳腺癌转移启动过程中的作用和调节(Robert Benezra，Ph.D.)，(3)用PI3K通路抑制剂治疗晚期乳腺癌的基于机制的策略的开发(Neal Rosen，Ph.D.和Sarat Chandarrupty，M.D.)。和(4)RND1介导的乳腺癌抑制(Filippo G.Giancotti，M.D.，Ph.D.)。行政核心A将由拉里·诺顿医学博士领导，他也是该计划的首席调查员。用于乳腺癌研究的RNAi工具的核心B将由Scott Lowe博士领导。

DESCRIPTION (provided by applicant): Proposed is a continuation of a productive, integrated, innovative Program Project in animal and laboratory models of breast cancer with actual and prospective clinical translatability. The goal is to address fundamental biological questions to advance our knowledge of metastasis and aberrant growth regulation and thereby improve all aspects of breast cancer prognostication, prediction of therapeutic benefit, and treatment. It is comprised of four projects, each led by a leader in the field, an Administrative Core to provide oversight and management, and a highly innovative RNAi Core to provide critical reagents as well as genetically engineered mouse models. Avoidance of duplication of effort, intellectual and material synergy, and orientation toward real clinical needs are hallmarks of this effort. The Projects and their Principal Investigators are: (1) TGF-beta, PI3K and HER2 pathways in breast cancer metastasis (Joan Massague, Ph.D.), (2) Role and regulation of Id1 during breast cancer metastasis initiation (Robert Benezra, Ph.D.), (3) Development of mechanism-based strategies for the treatment of advanced breast cancer with PI3K pathway inhibitors (Neal Rosen, Ph.D. and Sarat Chandarlapaty, M.D.)' and (4) RND1 - Mediated breast cancer suppression (Filippo G. Giancotti, M.D., Ph.D.). Administrative Core A is to be led by Larry Norton, M.D., who is also the Principal investigator of the Program. The Core B in RNAi Tools for Breast Cancer Research is to be led by Scott Lowe, Ph.D.