The Physical Microenvironment in Cancer Biology and Therapy

我们的总体目标是开发一个综合的、多学科的研究计划，将数学方法应用于研究肿瘤生物学和临床肿瘤学中的问题。无论是在智力上还是在教育上，最大的挑战是将生物数据和数学模型整合到一个概念框架中，该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，将在规划赠款的有效期内追求以下具体目标：项目1：摆脱稳态：癌症发生的综合数学和实验调查将侧重于肿瘤细胞的启动、促进和进展，特别关注不断演变的肿瘤种群与微环境要素的相互作用。大部分相应的实验工作将是在体外进行的。项目2：生理微环境及其在肿瘤侵袭和转移中的作用将侧重于癌细胞表型进化与肿瘤微环境的相互作用，包括成纤维细胞、血管和物理参数，如氧、葡萄糖和H“浓度。相应的实验研究将在很大程度上在体内进行，特别是使用窗口室。项目3：临床癌症成像的环境驱动数学建模将侧重于在成像分辨率被限制在几毫米且只能通过偶尔的成像会议获得时间变化的环境中对肿瘤生长和治疗反应进行建模的挑战。在每个项目中，研究将由一组数学家和实验者进行，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.