The basis of this proposal is integration of mathematics and experimental observations in cancer. As a result, mathematical expertise is distributed throughout every component. To support and expand the application integrated mathematical oncology, we will form a computational/mathematical core that will serve the research projects as well as the educational and outreach component of the PS-OC through the following: 1. Provide advanced computational technology, methods, and expertise. 2. Expertise in ecology and evolutionary biology and associated mathematical models 3. Facilitate collaborations among members of the PS-OC and with experimentalists, clinicians, mathematicians, physicists and other scientists who wish to use or learn more about integrated mathematical oncology. The core will purchase and maintain an advanced computing infrastructure that will be available to the members of the PS-OC for computationally demanding projects. It will hire a computer scientist to maintain the facility and assist members with its utilization. Since somatic evolution is the source of many of the dynamical changes in both in-situ and invasive cancer, he core will provide expertise in Danwinian dynamics to the PS-OC through consultants who are experts in the principles of ecology and evolution and experienced in application of evolutionary models to a wide range of biological systems including cancer. Finally, the core will encourage new collaborations by employing a

Public Health Relevance

While there is extensive mathematical expertise throughout the PS-OC, core facilities in computation will provide expertise and reduce expenses. Similarly, while somatic evolution is a major focus of the work in the proposed projects, none of the members of the PS-OC have formal training in ecology or evolutionary biology. Thus, consultants with expertise in the principle of Darwinian dynamics as well as modeling of those processes are essential. Finally, the core addresses one of the major questions and impediments to collaborations between mathematicians and tumor biologists/oncologists -

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143970-04
Application #
8555192
Study Section
Special Emphasis Panel (ZCA1-SRLB-9 (O1))
Project Start
2009-09-30
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$279,701
Indirect Cost
$99,744
Name
H. Lee Moffitt Cancer Center & Research Institute
Department
Type
DUNS #
139301956
City
Tampa
State
FL
Country
United States
Zip Code
33612
Gatenby, Robert; Brown, Joel (2018) The Evolution and Ecology of Resistance in Cancer Therapy. Cold Spring Harb Perspect Med 8:
Gravenmier, Curtis A; Siddique, Miriam; Gatenby, Robert A (2018) Adaptation to Stochastic Temporal Variations in Intratumoral Blood Flow: The Warburg Effect as a Bet Hedging Strategy. Bull Math Biol 80:954-970
Ibrahim-Hashim, Arig; Robertson-Tessi, Mark; Enriquez-Navas, Pedro M et al. (2017) Defining Cancer Subpopulations by Adaptive Strategies Rather Than Molecular Properties Provides Novel Insights into Intratumoral Evolution. Cancer Res 77:2242-2254
Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A (2017) Aggregation Effects and Population-Based Dynamics as a Source of Therapy Resistance in Cancer. IEEE Trans Biomed Eng 64:512-518
Perfahl, Holger; Hughes, Barry D; Alarcón, Tomás et al. (2017) 3D hybrid modelling of vascular network formation. J Theor Biol 414:254-268
de Groot, Amber E; Roy, Sounak; Brown, Joel S et al. (2017) Revisiting Seed and Soil: Examining the Primary Tumor and Cancer Cell Foraging in Metastasis. Mol Cancer Res 15:361-370
Gatenby, Robert A; Frieden, B Roy (2017) Cellular information dynamics through transmembrane flow of ions. Sci Rep 7:15075
McFarland, Christopher D; Yaglom, Julia A; Wojtkowiak, Jonathan W et al. (2017) The Damaging Effect of Passenger Mutations on Cancer Progression. Cancer Res 77:4763-4772
Zhang, Jingsong; Cunningham, Jessica J; Brown, Joel S et al. (2017) Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer. Nat Commun 8:1816
Zhang, Xiaomeng; Wojtkowiak, Jonathan W; Martinez, Gary V et al. (2016) MR Imaging Biomarkers to Monitor Early Response to Hypoxia-Activated Prodrug TH-302 in Pancreatic Cancer Xenografts. PLoS One 11:e0155289

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