Center for the """"""""Development of a Virtual Tumor ('CViT')"""""""". Due to the inherent non-linearity and complexity of the many networked physiological processes involved on the cellular level alone, conventional reductionism-driven approaches fail if one plans to investigate how for example genetic mutations affect multicellular behavior or how spatial-temporal patterns of angiogenesis impact the efficacy of cancer therapies. Given the multi-scaled pathophysiology involved, it is becoming abundantly clear that cancer research requires a complex systems science approach. This P20 planning grant application brings together a multi-institutional, interdisciplinary group of investigators with track records in either the biomedical or the computational aspects of cancer research, or both. The goals for the Exploratory P20 phase are as follows:
(AIM 1) to first establish an efficient infrastructure and workflow between the multiple teams, (AIM 2) to then collect, classify and archive the already developed modeling tools and techniques (i.e., building a digital model repository), and finally, (AIM 3) to initiate a pilot project, which connects and integrates three distinct modeling modules and platforms in order to test the hypothesis that molecular heterogeneity can quantitatively affect multicellular patterns. To accomplish these goals over the proposed three years, the team is structured into three cores: A) the administrative core, B) the computational modeling core (responsible for algorithm development and design of the digital model repository), and C) the biomedical data core (responsible for data collection and evaluation). The administrative core is guiding the ambitious effort and as such also responsible for organizing workshops and for seeking affiliations with educational and training programs as well as with other academic, governmental or corporate biomedical informatics groups and initiatives ('outreach and dissemination'). Anticipated success in this exploratory P20 phase during Year 1 and 2 will position CViT uniquely for a P50 Center application in its Year 3. The long term goal of CViT's P50 phase is to develop a generic tool-kit for modeling and simulating selected cancer types of interest such as breast, brain cancer, and melanoma following a paradigm-shifting cross-disciplinary complex systems approach. Combined with cutting edge biomedical data, this modeling tool-kit will allow cancer researchers to properly study cancer initiation and such critically linked progression features as invasion, angiogenesis and metastasis in the context of an emergent system. Ultimately, this module-based tool-kit will have important clinical applications including virtual trials and patient outcome predictions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory Grants--Cooperative Agreements (U56)
Project #
5U56CA113004-02
Application #
6954703
Study Section
Special Emphasis Panel (ZCA1-GRB-V (O1))
Program Officer
Gallahan, Daniel L
Project Start
2004-09-30
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$615,609
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
McGillen, Jessica B; Gaffney, Eamonn A; Martin, Natasha K et al. (2014) A general reaction-diffusion model of acidity in cancer invasion. J Math Biol 68:1199-224
Wang, Zhihui; Sagotsky, Jonathan; Taylor, Thomas et al. (2013) Accelerating cancer systems biology research through Semantic Web technology. Wiley Interdiscip Rev Syst Biol Med 5:135-51
Axelrod, David E; Shah, Kinsuk; Yang, Qifeng et al. (2012) Prognosis for Survival of Young Women with Breast Cancer by Quantitative p53 Immunohistochemistry. Cancer Clin Oncol 1:52-64
Wang, Zhihui; Bordas, Veronika; Sagotsky, Jonathan et al. (2012) Identifying therapeutic targets in a combined EGFR-TGF?R signalling cascade using a multiscale agent-based cancer model. Math Med Biol 29:95-108
Martin, N K; Robey, I F; Gaffney, E A et al. (2012) Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study. Br J Cancer 106:1280-7
Martin, Natasha K; Gaffney, Eamonn A; Gatenby, Robert A et al. (2011) A mathematical model of tumour and blood pHe regulation: The HCO3-/CO2 buffering system. Math Biosci 230:1-11
Deisboeck, Thomas S; Wang, Zhihui; Macklin, Paul et al. (2011) Multiscale cancer modeling. Annu Rev Biomed Eng 13:127-55
Murray, Philip J; Walter, Alex; Fletcher, Alexander G et al. (2011) Comparing a discrete and continuum model of the intestinal crypt. Phys Biol 8:026011
Wang, Zhihui; Bordas, Veronika; Deisboeck, Thomas S (2011) Discovering Molecular Targets in Cancer with Multiscale Modeling. Drug Dev Res 72:45-52
Smallbone, Kieran; Maini, Philip K; Gatenby, Robert A (2010) Episodic, transient systemic acidosis delays evolution of the malignant phenotype: Possible mechanism for cancer prevention by increased physical activity. Biol Direct 5:22

Showing the most recent 10 out of 44 publications