Oduola Wasiu Opeyemi, Li Xiangfang, Duan Chang, Qian Lijun, Wu Fen, Dougherty Edward R
Department of Electrical and Computer Engineering, Prairie View A&M University, Prairie View, TX, USA.
Department of Mechanical Engineering, Prairie View A&M University, Prairie View, TX, USA.
Cancer Inform. 2017 May 10;16:1176935117706888. doi: 10.1177/1176935117706888. eCollection 2017.
As cancer growth and development typically involves multiple genes and pathways, combination therapy has been touted as the standard of care in the treatment of cancer. However, drug toxicity becomes a major concern whenever a patient takes 2 or more drugs simultaneously at the maximum tolerable dosage. A potential solution would be administering the drugs in a sequential or alternating manner rather than concurrently. This study therefore examines the feasibility of such an approach from a switched system control perspective. Particularly, we study how genetic regulatory systems respond to sequential (switched) drug inputs using the time-based switching mechanism. The design of the time-driven drug switching function guarantees the stability of the genetic regulatory system and the repression of the diseased genes. Simulation results using proof-of-concept models and the proliferation and survival pathways with sequential drug inputs show the effectiveness of the proposed approach.
由于癌症的生长和发展通常涉及多个基因和信号通路，联合疗法已被吹捧为癌症治疗的标准治疗方法。然而，每当患者以最大耐受剂量同时服用两种或更多种药物时，药物毒性就会成为一个主要问题。一个潜在的解决方案是以序贯或交替的方式给药，而不是同时给药。因此，本研究从切换系统控制的角度研究了这种方法的可行性。特别是，我们使用基于时间的切换机制研究了基因调控系统如何对序贯（切换）药物输入做出反应。时间驱动药物切换函数的设计保证了基因调控系统的稳定性和患病基因的抑制。使用概念验证模型以及序贯药物输入的增殖和生存信号通路的模拟结果表明了所提出方法的有效性。
