Systems pharmacology approaches for optimization of antiangiogenic therapies: challenges and opportunities.

摘要: Targeted therapies have become an important therapeutic paradigm for multiple malignancies. The rapid development of resistance to these impedes the successful management advanced cancer. Due redundancy in angiogenic signaling, alternative proangiogenic factors are activated upon treatment with anti-VEGF agents. Higher doses agents lead greater stimulation compensatory pathways that limit efficacy VEGF-targeted drugs and produce escape mechanisms tumor. Evidence suggests dose intensity schedules affect dynamics this resistance. Thus, optimal dosing regimen is crucial maximizing benefit antiangiogenic limiting A systems pharmacology approach using multiscale computational modeling can facilitate a mechanistic understanding biomarkers their impacts on tumor reduction Herein, we discuss integrating biology therapy resistance, including circulating biomarkers, pharmacodynamics enable optimization gains.