CAREER: Stochastic Models of Cancer Evolution

职业：癌症进化的随机模型

• 批准号: 1349724
• 负责人: Jasmine Foo
• 金额: $ 40.01万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1349724&HistoricalAwards=false
• 关键词: CAREER; Stochastic; Models; Cancer; Evolution

This project will develop rigorous mathematical frameworks for understanding cancer initiation from healthy tissue, and the role of the tumor microenvironment on the evolution of resistance to anti-cancer therapies. In its first phase, this project will build stochastic models describing the evolutionary processes of reproduction, death and mutation in a spatially structured population, using stochastic interacting particle systems and mesoscopic approximations of these processes. These models will be analyzed to investigate how spatial population structure impacts the cancer initiation process and resulting genetic heterogeneity of the tissue. In its second phase, this project will develop mathematical models of the feedback between the evolving tumor cell population and its environment, using non-Markovian branching processes. These models will be analyzed to help elucidate the role of the tumor environment in the evolution of drug resistance. The PI will collaborate with cancer biologist to parametrize and validate these models a lung cancer experimental system. This research investigates how cancer evolution is shaped by environmental pressures and spatial population structure. This research can lead to the development of better statistical tools for assessment of cancer risk from premalignant fields, survival prediction, evaluation of treatment efficacy, and improved design of treatment regimens to prevent or delay drug resistance. The mathematical frameworks developed in this proposal will also be broadly applicable to understanding similar issues in ecology and disease dynamics, e.g. emergence of antibiotic resistance in bacterial or viral populations, or the geographic spread of invasive plant species and pesticide resistant weeds. An education goal of this project is to increase the representation of women in mathematics, with an emphasis on recruitment into the mathematical biology and medicine. A week-long summer program will be held each year at the University of Minnesota for local high school girls with the theme of "Mathematics in Biology and Medicine." In addition, a workshop will be held to bring together early career women in mathematical biology with the aim of sharing research and discussing emerging areas of the field, and undergraduate students will be integrated into the proposed research efforts for year-long projects. These programs will be linked through the development of an online community to provide support, networking and guidance to alumni, as they continue pursuing their goals beyond these programs.

该项目将开发严格的数学框架，以了解从健康组织开始的癌症，以及肿瘤微环境在抗癌治疗耐药性演变中的作用。在第一阶段，这个项目将使用随机相互作用的粒子系统和这些过程的介观近似来建立描述空间结构种群中繁殖、死亡和突变的进化过程的随机模型。将对这些模型进行分析，以调查空间种群结构如何影响癌症启动过程和由此导致的组织遗传异质性。在第二阶段，该项目将利用非马尔科夫分支过程，建立不断演变的肿瘤细胞种群与其环境之间反馈的数学模型。这些模型将被分析，以帮助阐明肿瘤环境在耐药性演变中的作用。PI将与癌症生物学家合作，将这些模型作为肺癌实验系统进行参数化和验证。这项研究调查了环境压力和空间人口结构是如何塑造癌症进化的。这项研究可以开发出更好的统计工具，从癌前领域评估癌症风险，预测生存，评估治疗效果，并改进治疗方案的设计，以防止或延缓耐药性。这项建议中建立的数学框架也将广泛适用于理解生态学和疾病动力学中的类似问题，例如细菌或病毒种群中出现的抗生素抗药性，或入侵植物物种和抗药性杂草的地理传播。该项目的一个教育目标是增加妇女在数学领域的代表性，重点是招募妇女进入数学生物学和医学领域。明尼苏达大学每年都会为当地高中女生举办为期一周的暑期课程，主题是“生物和医学中的数学”。此外，还将举办一次讲习班，将数学生物学领域的早期职业女性聚集在一起，目的是分享研究和讨论该领域的新兴领域，本科生将被纳入为期一年的项目的拟议研究工作。这些计划将通过发展一个在线社区联系在一起，为校友提供支持、网络和指导，因为他们继续追求这些计划以外的目标。