Modeling Competitive Dynamics Between Healthy and Cancerous Liver Cells with Yes-Associated Protein (YAP) Hyperactivation

Current treatments for hepatocellular carcinoma (HCC) include partial hepatectomy (PH), where two-thirds of the liver is removed. However, when some cancer remains after PH, competition for resources and survival occurs between healthy and cancerous cells. Recent studies suggest that hyperactivation of yes-associated protein (YAP) could be a non-invasive treatment option for HCC. In this study, we propose two simple ordinary differential equation models of resource competition in HCC livers after PH, one capturing the natural dynamics of resource competition between healthy and cancer cells and the other incorporating YAP hyperactivation therapy. We perform full qualitative and quantitative analyses of these models and validate them on experimental data. Our numerical simulations reveal that treatment schedules must be prescribed based on a patient’s tumor aggression. We also found that a high dose of treatment is necessary to completely clear a tumor in all patients, leading us to suggest prescribing YAP hyperactivation therapy in lower doses with other treatments for HCC for the best patient outcomes.