Supplementary Materials

Supplementary Materials for:

Computational Modeling of ERBB2-Amplified Breast Cancer Identifies Combined ErbB2/3 Blockade as Superior to the Combination of MEK
and AKT Inhibitors

Daniel C. Kirouac,* Jin Y. Du, Johanna Lahdenranta, Ryan Overland, Defne Yarar, Violette Paragas, Emily Pace, Charlotte F. McDonagh, Ulrik B. Nielsen, Matthew D. Onsum

*Corresponding author. E-mail: dkirouac@merrimackpharma.com

This PDF file includes:

  • Fig. S1. Time-course proteomic responses to MM-111 and lapatinib treatment.
  • Fig. S2. Relative abundance of total ErbB3 versus phosphorylated AKT and ERK in response to MM-111 and lapatinib combination treatments.
  • Fig. S3. Molecular responses to PI3K and MEK inhibition across a panel of 20 cell lines.
  • Fig. S4. Simulated ErbB3-mediated crosstalk between PI3K/AKT and MAPK/ERK pathways.
  • Fig. S5. Transcriptional feedback circuits regulate ErbB3 abundance and activation.
  • Fig. S6. Weighted sum squared error (WSSE) for nine alternative logic models of cell growth.
  • Fig. S7. Functional significance of feedback circuits.
  • Fig. S8. Mutational status and relative resistance or sensitivity to combination drug treatment.
  • Fig. S9. Cell-surface abundance of ErbB2 and ErbB3 is not affected by MM-111 treatment.
  • Fig. S10. Correlations between total ErbB2, ErbB3, and phosphorylated ErbB2 abundance across a panel of 82 cancer cell lines.
  • Fig. S11. Simulation of lapatinib pharmacokinetics over a range of oral absorption (ka) rates.
  • Table S1. Model variables.
  • Table S2. Model parameters.
  • Table S3. Antibodies used in Luminex assays.
  • Table S4. Cell lines included in basal protein profiling.

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Citation: D. C. Kirouac, J. Y. Du, J. Lahdenranta, R. Overland, D. Yarar, V. Paragas, E. Pace, C. F. McDonagh, U. B. Nielsen, M. D. Onsum, Computational Modeling of ERBB2-Amplified Breast Cancer Identifies Combined ErbB2/3 Blockade as Superior to the Combination of MEK and AKT Inhibitors. Sci. Signal. 6, ra68 (2013).

© 2013 American Association for the Advancement of Science