Sequential Therapeutic Response Modeling for Tumor Treatment Using Computational Hybrid Control Systems Approach
Sequential Therapeutic Response Modeling for Tumor Treatment Using Computational Hybrid Control Systems Approach
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DOI：
10.1109/tbme.2017.2723957
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发表时间：
2018-04
影响因子：
4.6
通讯作者：
W. Oduola;Xiangfang Li;C. Duan;Lijun Qian;E. Dougherty
中科院分区：
文献类型：
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作者：
W. Oduola;Xiangfang Li;C. Duan;Lijun Qian;E. Dougherty
目的：肿瘤的发生是由于细胞群增殖控制的突变和改变引起的不受控制的细胞分裂。与肿瘤生长和发展的斗争往往依赖于联合治疗，这已被公认为癌症治疗和预防药物相关耐药性的主要护理标准之一。当患者以最大耐受剂量同时服用两种或两种以上药物时，组合药物的毒性引起了重大关注。在肿瘤治疗中，一个很有希望的解决方案是以交替或顺序的方式而不是同时的方式给药。在本文中，我们从数学的角度研究了这种方法的可行性，并提出了一个切换混合控制系统框架。方法：利用时间依赖的切换策略，研究肿瘤细胞动力学对顺序给药的反应。采用转运区隔化模型描述肿瘤细胞进展至死亡。结果：基于时间的药物切换逻辑设计确保了肿瘤细胞增殖受到抑制。结论：采用连续服药的肿瘤生长动态模拟结果，证明了所提出的方法在减小肿瘤大小方面的有效性。意义：本文首次尝试为生物医学研究人员和临床医生提供时序给药的切换混合控制系统框架。
Objective: Tumorigenesis is due to uncontrolled cell division arising from mutations and alterations in the proliferative controls of the cell population. The fight against tumor growth and development has often relied on combination therapy that has been acclaimed as one of the main standards of care in cancer therapeutics and prevention of drug-related resistances. The toxicity of the combinatorial drugs raises a significant concern whenever patients take two or more drugs concurrently at the maximum tolerated dose. A promising solution in tumor treatment involves the administration of the drugs in an alternating or sequential fashion rather than a simultaneous manner. In this paper, we investigate how feasible such an approach is from a mathematical perspective and propose a switched hybrid control systems framework. Methods: We explore the response of tumor cells dynamics to sequential drugs administration with the aid of a time-dependent switching strategy. A transit compartmentalized model is employed to describe the tumor cells progression to death. Results: The design of the time-based drug switching logic ensures the proliferating tumor cells are repressed. Conclusions: Simulation results are provided using the tumor growth dynamics with sequential drugs intake to demonstrate the effectiveness of the proposed method in reducing the tumor size. Significance: This paper is the first attempt to provide a switched hybrid control systems framework on sequential drug administration to biomedical researchers and clinicians.