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: Lapatinib kills most cells but 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 HER2 Lapatinib PDK1 AKT (PKB) 14-3-3 ER FoxO PI3K p p p p Translocation FoxO Apoptotic genes Transcription Translocation Protein Translation

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

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

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?