Hendrata Melisa, Sudiono Janti
Department of Mathematics, California State University, Los Angeles, CA, USA.
Department of Oral Pathology, Faculty of Dentistry, Trisakti University, Jakarta, Indonesia.
In Silico Biol. 2021;14(3-4):71-88. doi: 10.3233/ISB-210235.
Vascular endothelial growth factor (VEGF) has been known as a key mediator of angiogenesis in cancer. Bevacizumab is anti-VEGF monoclonal antibody that has been approved by the FDA as a first-line treatment in many types of cancer. In this paper, we extend a previously validated multiscale tumor model to comprehensively include the multiple roles of VEGF during the course of angiogenesis and its binding mechanism with bevacizumab. We use the model to simulate tumor system response under various bevacizumab concentrations, both in stand-alone treatment and in combination with chemotherapy. Our simulation indicates that periodic administration of bevacizumab with lower concentration can achieve greater efficacy than a single treatment with higher concentration. The simulation of the combined therapy also shows that the continuous administration of bevacizumab during the maintenance phase can lead to antitumor activity which further suppresses its growth. Agreement with experimental results indicates the potential of the model in predicting the efficacy of anti-VEGF therapies and could therefore contribute to developing prospective clinical trials.
血管内皮生长因子（VEGF）一直被认为是癌症血管生成的关键介质。贝伐单抗是一种抗VEGF单克隆抗体，已被美国食品药品监督管理局（FDA）批准作为多种癌症的一线治疗药物。在本文中，我们扩展了先前验证的多尺度肿瘤模型，以全面纳入VEGF在血管生成过程中的多种作用及其与贝伐单抗的结合机制。我们使用该模型模拟在各种贝伐单抗浓度下肿瘤系统的反应，包括单独治疗和与化疗联合治疗。我们的模拟表明，低浓度贝伐单抗的定期给药比高浓度的单次治疗能取得更大的疗效。联合治疗的模拟还表明，在维持阶段持续给予贝伐单抗可产生抗肿瘤活性，进一步抑制肿瘤生长。与实验结果的一致性表明该模型在预测抗VEGF治疗疗效方面的潜力，因此有助于开展前瞻性临床试验。
