The Physical Microenvironment in Cancer Biology and Therapy

我们的总体目标是发展一个综合的、多学科的研究项目，应用数学方法来研究肿瘤生物学和临床肿瘤学中的问题。在智力上和教育上，最大的挑战是将生物学数据和数学模型整合到一个概念框架中，这个概念框架可以涵盖肿瘤生物学中可观察到的细胞和细胞外动力学。为了实现这一目标，将在计划拨款的整个生命周期内追求以下具体目标：项目1：逃离稳态：癌症发生的综合数学和实验研究将重点放在肿瘤细胞的起始、促进和进展上，特别关注肿瘤种群与微环境元素的相互作用。大部分相应的实验工作将在体外进行。项目2:The Physiological Microenvironment and its role in Tumor Invasion and Metastases将重点研究肿瘤细胞表型进化与肿瘤微环境（包括成纤维细胞、血管以及氧、葡萄糖和H”浓度等物理参数）的相互作用。相应的实证研究将主要在体内进行，特别是使用窗室。项目3：临床癌症成像的环境驱动数学建模将重点关注在成像分辨率限制在几毫米的环境中模拟肿瘤生长和对治疗的反应，并且只能通过偶尔的成像会议获得时间变化。在每个项目中，研究将由数学家和实验学家组成的团队进行，并将重点放在系统动力学上，特别是肿瘤表型进化和不断变化的微环境之间的相互作用。

Our overall goal is to develop an integrative, multidisciplinary research program that applies mathematical methods to the investigation of problem in tumor biology and clinical oncology. The great challenge - both intellectually and educationally - is to integrate biological data and mathematical models into a conceptual framework that can encompass observable cellular and extracellular dynamics in tumor biology. To achieve this goal the following specific aims will be pursued during the life-time of the planning grant: Project 1: Escape from Homeostasis: Integrated mathematical and experimental investigation of carcinogenesis will focus on tumor cell initiation promotion and progression with particular focus on the interactions of the evolving tumor populations with elements of the microenvironment. Most of this corresponding experimental work will be in-vitro. Project 2 : The Physiological Microenvironment and its role in Tumor Invasion and Metastases will focus on the mutual interactions of cancer cell phenotypic evolution with the tumor microenvironment including fibroblasts, blood vessels, and physical parameters such as oxygen, glucose and H" concentrations. The corresponding empirical research will be largely carried out in-vivo particularly using window chambers. Project 3: Environment-driven Mathematical modeling for Clinical Cancer imaging will focus on the challenge modeling tumor growth and response to therapy in an environment in which imaging resolution is restricted to a few mm and temporal variations obtainable only through occasional imaging sessions. n each project the research will be carried out by a team of mathematicians and experimentalists and will focus on system dynamics, particularly on the mutually interactions of tumor phenotypic evolution and the changing microenvironment.