IEEE Trans Biomed Eng. 2018 Apr;65(4):866-874. doi: 10.1109/TBME.2017.2723957. Epub 2017 Jul 6.
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.
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.
The design of the time-based drug switching logic ensures the proliferating tumor cells are repressed.
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.
This paper is the first attempt to provide a switched hybrid control systems framework on sequential drug administration to biomedical researchers and clinicians.
肿瘤的发生是由于细胞群体增殖控制的突变和改变导致的不受控制的细胞分裂。对抗肿瘤生长和发展的斗争常常依赖于联合治疗，这被认为是癌症治疗和预防药物相关耐药性的主要护理标准之一。联合用药的毒性引起了人们的极大关注，因为患者在最大耐受剂量下同时服用两种或两种以上药物。肿瘤治疗中一个有前途的解决方案是交替或顺序给药，而不是同时给药。在本文中，我们从数学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。
我们借助时变切换策略来研究肿瘤细胞动力学对序贯药物给药的反应。采用转移隔室模型来描述肿瘤细胞向死亡的进展。
基于时间的药物切换逻辑的设计确保了增殖的肿瘤细胞受到抑制。
使用序贯药物摄入的肿瘤生长动力学提供了仿真结果，以证明所提出的方法在减小肿瘤体积方面的有效性。
本文首次尝试为生物医学研究人员和临床医生提供序贯药物给药的切换混合控制系统框架。
