癌症细胞动力学的模型预测控制:一种新的治疗设计策略

Benjamin Smart, Irene de Cesare, L. Renson, L. Marucci
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引用次数: 1

摘要

网络遗传学的最新进展导致了新的计算和实验平台的开发,使我们能够通过应用外部反馈控制来稳健地控制细胞动力学。这种技术从未被应用于调节癌症细胞的细胞内动力学。在此,我们在计算机上表明,自适应模型预测控制(MPC)可以有效地用于引导非小细胞肺癌(NSCLC)细胞的模拟信号动力学,使其类似于野生型细胞。我们基于优化的控制算法能够调整成本函数,迫使控制器更换不同的药物和/或减少药物暴露,最大限度地减少药物诱导的毒性和治疗耐药性。我们的研究结果为癌症细胞中新的网络遗传学实验铺平了道路,从长远来看,可以支持生物医学应用中改进药物组合疗法的设计。
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Model predictive control of cancer cellular dynamics: a new strategy for therapy design
Recent advancements in cybergenetics have led to the development of new computational and experimental platforms that enable us to robustly steer cellular dynamics by applying external feedback control. Such technologies have never been applied to regulate intracellular dynamics of cancer cells. Here, we show in silico that adaptive model predictive control (MPC) can effectively be used to steer the simulated signalling dynamics of Non-Small Cell Lung Cancer (NSCLC) cells to resemble those of wild type cells. Our optimisation-based control algorithm enables tailoring the cost function to force the controller to alternate different drugs and/or reduce drug exposure, minimising both drug-induced toxicity and resistance to treatment. Our results pave the way for new cybergenetics experiments in cancer cells, and, longer term, can support the design of improved drug combination therapies in biomedical applications.
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