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Modeling of Acute R esistance to the HER2 Inhibitor , L apatinib , in Breast C ancer C ells

Modeling of Acute R esistance to the HER2 Inhibitor , L apatinib , in Breast C ancer C ells. Marc Fink & Yan Liu Student Project Proposal Computational Cell Biology 2012. Motivation. Observation during experiments : Lapatinib kills most cells but some of them can survive.

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Modeling of Acute R esistance to the HER2 Inhibitor , L apatinib , in Breast C ancer C ells

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  1. Modeling of Acute Resistance to the HER2 Inhibitor, Lapatinib, in Breast Cancer Cells Marc Fink & Yan Liu Student Project Proposal Computational Cell Biology 2012

  2. Motivation Observation during experiments: Lapatinibkills most cellsbut some of them can survive. Hypothesis: Secondary receptor pathways leads to cell survival. Goal: Regenerate the experimental results with mathematical model and find out the factors which influence the percentage of cell survival

  3. Mechanistic (process) diagrams Lapatinib HER2 PI3K PDK1 p Protein Translation AKT (PKB) p ER FoxO p FoxO p 14-3-3 Translocation Translocation Transcription FoxO FoxO Apoptotic genes

  4. Mechanistic (process) diagrams Lapatinib Lapatinib HER2 PI3K PDK1 p Protein Translation AKT (PKB) p ER FoxO p FoxO p 14-3-3 Translocation Translocation Transcription FoxO FoxO Apoptotic genes FoxO FoxO Survival genes

  5. Mechanistic (process) diagrams Death Lapatinib ?????? HER2 Survival PI3K PDK1 p Protein Translation AKT (PKB) p ER FoxO p FoxO p 14-3-3 Translocation Translocation Transcription FoxO FoxO Apoptotic genes FoxO FoxO Survival genes

  6. Kinetic model equations [Park, Schneider, Haugh, 2003]

  7. Working schedule • Finish and modify the mechanistic diagrams • Build up model in Vcell or Matlab • Compare simulation results with experimental results • Analyze the model and estimate/tune parameters • Consider stochastic model, if necessary • Analyze the results • Documentation of the project

  8. Questions and Suggestions?

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