Explosive Evolution Under Stress: The Driving Forces of Cancer Dynamics (Main)

压力下的爆炸性进化：癌症动力学的驱动力（主）

• 批准号: 8535630
• 负责人: Robert H. Austin
• 金额: $ 247.98万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8535630
• 关键词: Biology; Cancer Control; Cells; Ecology; Evolution; Genomics; Habitats; Instruction; Malignant Neoplasms; Microfabrication; Nanotechnology; Physics; Proteomics; Recurrence; Resistance; Stress; Techniques; Technology; Testing; cancer cell; cancer therapy; driving force; oncology

The re-emergence of resistant cancer cells after initial therapy is one of the great unsolved, and deadly, problems in oncology, and a fundamental problem of evolution under stress. This project is aimed at understanding, from general principles of physics, ecology, and biology, why recurrence of resistant cancer cells seems to be a universal phenomenon in cancer. We believe that evolution in small, stressed habitats is the key to the rapid and inevitable re-emergence of resistance. The physical technology that drives this Project uses microfabrication of tiny, stressed habitats to test these Ideas. Modern techniques of physical probes, genomics, proteomics and nanotechnology will allow us to analyze the evolutionary path of these emergent resistant cells.

耐药癌细胞在最初的治疗后重新出现，是肿瘤学中尚未解决的、致命的重大问题之一，也是应激下进化的根本问题。这个项目的目的是从物理学、生态学和生物学的一般原理来理解为什么耐药癌细胞的复发似乎是癌症中的普遍现象。我们认为，在小而紧张的栖息地中的进化是迅速和不可避免地重新出现耐药性的关键。推动这个项目的物理技术使用微小的、有压力的栖息地的微制造来测试这些想法。物理探针、基因组学、蛋白质组学和纳米技术的现代技术将使我们能够分析这些新出现的耐药细胞的进化路径。

项目成果

Stress-response protein RBM3 attenuates the stem-like properties of prostate cancer cells by interfering with CD44 variant splicing.

• DOI: 10.1158/0008-5472.can-12-1343
• 发表时间: 2013-05
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Yu Zeng;D. Wodzenski;D. Gao;T. Shiraishi;N. Terada;Youqiang Li;Donald J. Vander Griend;Jun Luo

You cannot tell a book by looking at the cover: Cryptic complexity in bacterial evolution.

你不能通过看封面来辨别一本书：细菌进化中的隐秘复杂性。

• DOI: 10.1063/1.4894410
• 发表时间: 2014
• 期刊: Biomicrofluidics
• 影响因子: 3.2
• 作者: Zhang,Qiucen;Bos,Julia;Tarnopolskiy,Grigory;Sturm,JamesC;Kim,Hyunsung;Pourmand,Nader;Austin,RobertH
• 通讯作者: Austin,RobertH

Emergent behaviors from a cellular automaton model for invasive tumor growth in heterogeneous microenvironments.

• DOI: 10.1371/journal.pcbi.1002314
• 发表时间: 2011-12
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Jiao Y;Torquato S
• 通讯作者: Torquato S

Evolutionary game theory in cancer: first steps in prediction of metastatic cancer progression?

癌症进化博弈论：预测转移性癌症进展的第一步？

• DOI: 10.2217/fon.15.5
• 发表时间: 2015
• 期刊: Future oncology (London, England)
• 作者: Wu,Amy;Liao,David;Austin,Robert
• 通讯作者: Austin,Robert

The Goldilocks principle and antibiotic resistance in bacteria.

金发姑娘原理和细菌的抗生素耐药性。

• DOI: 10.1021/mp200274r
• 发表时间: 2011
• 期刊: Molecular pharmaceutics
• 影响因子: 4.9
• 作者: Zhang,Qiucen;Robin,Kristelle;Liao,David;Lambert,Guillaume;Austin,RobertH
• 通讯作者: Austin,RobertH