Glioma differentiation therapy is a novel modality to increase anti-glioma effects using specific drugs to induce glioma cell differentiation to glia-like cells. However, the molecular mechanisms underlying glioma differentiation remain poorly understood. In this study, we built an experiment-integrated mathematical model for glioma differentiation signaling pathways. Our modeling and experimental analysis revealed that a "one-way-switch" bifurcation of cyclin D1 dynamics was critical for controlling the phenotypic transition of glioma cells. We also quantitatively evaluated drug combinations toward a synergistic therapeutic effect. These results provide insights into the molecular mechanisms underlying glioma differentiation and implications for the design of novel therapeutic targets in anti-cancer therapy.
Keywords: Cyclin D1; Glioma differentiation; Mathematical modeling; Phenotype switching.
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