Therapeutic implications of dickkopf affecting cancer stem cell fate

摘要

A method of determining a therapeutic regimen for the treatment of cancer with Dickkopf (Dkk) protein in which a mathematical model of differential equations describing the major signaling pathways involved in stem cell regulation is created and used to simulate signals from the cancer stem cell environment based upon administration of at least a single dose of Dkk in vitro and/or in vivo. A method of modulating cancer stem cells is also provided in which the stem cell computer model is simulates the effect of Dkk and performs a calibration test to determine a threshold value above which Dkk induces cell differentiation and a threshold value below which Dkk induces stem cell proliferation.

主权项

1. A method of modulating normal stem cells or cancer stem cells involved in cancer selected from the group consisting of breast cancer, colon cancer, leukemia, and melanoma, the method comprising:
creating a stem cell computer model for at least one signaling pathway involved in stem cell development, comprising a proliferating stem cell (SC) compartment and a differentiated cell (DC) compartment; simulating in a computer, an effect on the at least one signaling pathway of the stem cell computer model based upon data obtained from administration of at least a single dose of Dkk protein in vitro or in vivo; performing a calibration test based on the effect in the simulating step to determine a threshold Dkk concentration value above which administration of Dkk induces stem cell differentiation and a threshold Dkk concentration value below which administration of Dkk induces stem cell proliferation, wherein Dkk regulates stem cell differentiation and stem cell proliferation whereby a decrease in number of stem cells indicates stem cell differentiation and an increase in cellular growth indicates stem cell proliferation; inducing stem cell differentiation in normal or cancer stem cells with a dose of Dkk above the threshold Dkk concentration value indicative of stem cell differentiation, or inducing stem cell proliferation in normal or cancer stem cells with a dose of Dkk below the threshold Dkk concentration value indicative of stem cell proliferation.