math model for cancer micro env model
DESCRIPTION
This is a Journal club PPT for a math model for Cancer and its micro-EnvironmentTRANSCRIPT
A micro-environmental mode of carcinogenesis
Xu Zhou
Max Planck Institute for Complex Physics
SEMINAR "Principles of cancer development“, November 10, 2008
What causes Cancer? – cellular view
• Once it was taken as infectious disease
• Genetic disease of multi-cellular organism- Oncogenes - tumor suppressor genes
• Evolution vs. de-evolution
What microenvironment is important?
• Clone is cell reprogramming by changing microenvironment
• Normal breast epithelium cells => cancer cell by ECM-degrading enzyme
• Tumour microenvironment’s roles in in tumor development, start in 1960’s, now revived
“The tumour microenvironment—Introduction”, Seminars in Cancer Biology , 12, 2, 87-155, (2002)
What causes Cancer? – Environmental view
• Tumour microenvironment in driving tumorigenesis depend on somatic genetic alterations?
• Tumour microenvironment is independent from cancer cell gene mutation
“Tumour microenvironment: No changes necessary”, Nature Reviews Cancer 8, 324 – 325, (2008)
Cancer develops with the change of its microenvironment
• Cell with oncogene turning on => extra growth => still benign
• Balance with ECM structures destroyed => Cancer
• Cancer stem cells, epithelial-mesenchymal transition, increased angiogenesis and unrestrained cell growth may result from deregulation of tissue microenvironment
Hypothesis of micro-environment selection model
1) There is no cancer programming
2) cancer gene mutation under selection pressure of microenvironment
Waddinton’s epigenetic landscape
A warm-up: predator-prey model
MYKX
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Cancer Evolution model (I)
• A kinetic model with parameters Start
• Xi – number of different phenotypes
• Ki – need to contact with base
memberane
Cancer Evolution model (II)
• Cancer evolution
- proliferation away from base
membrane
- invasive
• Evolution dynamics change, leads to
different phenotypes
Evolution barriers vs. Cancer mutations
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Tumorigenesis vs. Dynamic system evolutions
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The good of the Model• A mathematical framework to
explain why phenotypes appear in certain pattern
• Parameters to associate hallmark of cancer mutations
• Cure cancer by re-engineering its microenvironment
What’s bad in the model• This is not new derived from this
model
• Each phenotype change is triggered by changing those parameters manually.
• i.e. I know what’s happening, then I put it into the model
Conclusions• Cancer is caused by genetic mutations
and environmental selections
• Cancer development can be modeled as evolution dynamic system, each phenotype corresponds to a certain evolution advantage in the micro-environment
• Cure cancer by re-engineering its microenvironment
Some key questions about cancer
• Multi-cellular disease
• Sth wrong with coordination of cells
• Of old age