A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment

PLoS Comput Biol. 2018 Jan 19;14(1):e1005920. doi: 10.1371/journal.pcbi.1005920. eCollection 2018 Jan.


Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics. By including the molecular details of IL-6 binding, we are able to quantify the temporal changes in fractional occupancies of bound receptors and their influence on tumor volume. There is a strong correlation between the model output and experimental data for primary tumor xenografts. We also used the model to predict tumor response to administration of the humanized IL-6R monoclonal antibody, tocilizumab (TCZ), and we found that as little as 1mg/kg of TCZ administered weekly for 7 weeks is sufficient to result in tumor reduction and a sustained deceleration of tumor growth.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Binding Sites
  • Cisplatin / pharmacology
  • Computer Simulation
  • Endothelial Cells / cytology
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology*
  • Mice
  • Mice, SCID
  • Models, Theoretical
  • Neoplasm Transplantation
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Phenotype
  • Receptors, Interleukin-6 / metabolism
  • Signal Transduction
  • Time Factors


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • IL6 protein, human
  • IL6R protein, human
  • Interleukin-6
  • Receptors, Interleukin-6
  • tocilizumab
  • Cisplatin