Inhibition of breast cancer growth by GM-CSF: A mathematical model
by
Barbara Szomolay
Mathematical Biosciences Institute, The Ohio State University
Coauthors: Tim D. Eubank, Ryan D. Roberts, Clay B. Marsh, Avner Friedman

GM-CSF is a drug that enhances the ability of macrophages to present antigen and initiate immune response. GM-CSF also stimulates monocytes to secrete soluble VEGF receptor (sVEGFR-1) which binds to and inactivates VEGF. Eubank and colleagues in a recent work discovered that GM-CSF treatment locally in murine breast cancers reduced tumor growth and metastasis; moreover, GM-CSF lowered oxygen level and reduced blood vessel density within the tumor. We developed a mathematical model which addresses the effect of GM-CSF on the growth of breast cancer in mice. The model takes into account the experimentally established interactions among cancer cells, macrophages, endothelial cells, VEGF and M-CSF. The model simulates the growth of tumor as a function of the local GM-CSF dose. The model simulations were validated against in vivo data and show a good fit with experimental results. We used the model to compare the efficacy of different dosing protocols of injection of GM-CSF, as well as to suggest new hypotheses for slowing the progression of breast tumor. For example, the model suggests that injecting the drug daily, twice or 3 times a week are comparably effective. In contrast, reducing or over increasing the frequency of dosing is counterproductive. We hope to further refine the model in future work, by including the interactions of macrophages and other immune cells, fibroblasts and cytokines that communicate between the tumor and its micro-environment.

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Date received: May 14, 2008