A robust optimal control framework for controlling aberrant RTK signaling pathways in esophageal cancer
A robust optimal control framework for controlling aberrant RTK signaling pathways in esophageal cancer
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DOI：
10.1007/s00285-023-02033-0
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发表时间：
2024-02-01
影响因子：
1.9
通讯作者：
Rana，Jashmon
中科院分区：
文献类型：
--
作者：
Roy，Souvik;Pan，Zui;Rana，Jashmon
这项研究提出了一个新的框架，以获得个性化的最佳治疗策略，针对异常信号通路在食管癌，如表皮生长因子（EGF）和血管内皮生长因子（VEGF）信号通路。考虑到这些信号机制的特定异质性，开发了一种新的药代动力学模型。最佳疗法设计为使用三步过程获得。首先，有限维约束优化问题被解决，以获得药代动力学模型的参数，使用离散的患者数据测量。接下来，进行灵敏度分析以确定哪些参数对EGF受体和VEGF受体的变体的演变敏感。最后，第二个最优控制问题的基础上解决的敏感性分析结果，使用修改后的药代动力学模型，其中包括两个代表性的药物曲妥珠单抗和贝伐单抗，分别针对EGF和VEGF。两种药物的组合的数值结果表明所提出的框架的效率。
This study presents a new framework for obtaining personalized optimal treatment strategies targeting aberrant signaling pathways in esophageal cancer, such as the epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) signaling pathways. A new pharmacokinetic model is developed taking into account specific heterogeneities of these signaling mechanisms. The optimal therapies are designed to be obtained using a three step process. First, a finite-dimensional constrained optimization problem is solved to obtain the parameters of the pharmacokinetic model, using discrete patient data measurements. Next, a sensitivity analysis is carried out to determine which of the parameters are sensitive to the evolution of the variants of EGF receptors and VEGF receptors. Finally, a second optimal control problem is solved based on the sensitivity analysis results, using a modified pharmacokinetic model that incorporates two representative drugs Trastuzumab and Bevacizumab, targeting EGF and VEGF, respectively. Numerical results with the combination of the two drugs demonstrate the efficiency of the proposed framework.