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Background: Breast cancer is one of the leading causes of mortality among women worldwide.As a potent multi-targeted receptor tyrosine kinase inhibitor, sunitinib has shown promising results in clinical trials of advanced breast cancer.However, it was reported that sunitinib could increase the population of cancer-stem-like cells (CSCs) in human breast cancer xenografts, thus limiting its effectiveness.In the effort to improve the therapeutic outcomes, we found that dopamine is a potential CSCs-targeting drug, which could greatly enhance the response of sunitinib in the treatment of drug-resistant breast cancer.Objective: This study aimed at establishing an integrated PK/PD model to quantitatively characterize the enhanced antitumor effect mediated by dopamine while taking into account the influence of the CSC frequency on the tumor burden.