Program Project in Models of Breast Cancer

描述（由申请人提供）：拟议的是一个生产性的，综合的，创新的计划项目在乳腺癌的动物和实验室模型与实际和前瞻性的临床可翻译性的延续。其目标是解决基本的生物学问题，以推进我们对转移和异常生长调节的认识，从而改善乳腺癌诊断、治疗益处预测和治疗的各个方面。它由四个项目组成，每个项目由该领域的领导者领导，一个行政核心提供监督和管理，一个高度创新的RNAi核心提供关键试剂以及基因工程小鼠模型。避免重复劳动，智力和物质的协同作用，以及面向真实的临床需求是其标志 这一努力。这些项目及其主要研究者是：（1）乳腺癌转移中的TGF-β、PI 3 K和HER 2通路（Joan Massague，Ph.D.），(2)Id 1在乳腺癌转移启动过程中的作用和调节（Robert Benezra，Ph.D.），(3)用PI 3 K通路抑制剂治疗晚期乳腺癌的基于机制的策略的开发（Neal罗森，Ph.D.和医学博士萨拉特·拉拉帕蒂（Sarat Zarlapaty））（4）RND 1介导的乳腺癌抑制（Filippo G.吉安科蒂医学博士Ph.D.）。行政核心A将由医学博士拉里·诺顿领导，他也是该项目的首席研究员。乳腺癌研究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.