A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment.
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ABSTRACT:
SUBMITTER: Nazari F
PROVIDER: S-EPMC5792033 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment.
Nazari Fereshteh F Pearson Alexander T AT Nör Jacques Eduardo JE Jackson Trachette L TL
PLoS computational biology 20180119 1
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 th ...[more]
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Project description:This a model from the article:
A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment
Fereshteh Nazari, Alexander T. Pearson, Jacques Eduardo Nor, Trachette L. Jackson. PloS Computational Biology, 2018 Jan.
Abstract:
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.
Author Summary:
A small population of cancer stem cells that share many of the biological characteristics of normal adult stem cells are believed to initiate and sustain tumor growth for a wide variety of malignancies. Growth and survival of these cancer stem cells is highly influenced by tumor micro-environmental factors and molecular signaling initiated by cytokines and growth factors. This work focuses on quantifying the influence of IL-6, a pleiotropic cytokine secreted by a variety of cell types, on cancer stem cell self-renewal and survival. We present a mathematical model for IL-6 mediated, cancer stem cell driven tumor growth that operates at the following levels: (1) the molecular level—capturing cell surface dynamics of receptor-ligand binding and receptor activation that lead to intra-cellular signal transduction cascades; and (2) the cellular level—describing tumor growth, cellular composition, and response to treatments targeted against IL-6.
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2024-09-02 | BIOMD0000000819 | BioModels
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