...
首页> 外文期刊>Frontiers in Bioengineering and Biotechnology >An Optimal Control Framework for the Automated Design of Personalized Cancer Treatments
【24h】

An Optimal Control Framework for the Automated Design of Personalized Cancer Treatments

机译:个性化癌症治疗自动设计的最优控制框架

获取原文
   

获取外文期刊封面封底 >>

       

摘要

One of the key challenges in current cancer research is the development of computational strategies to support clinicians in the identification of successful personalized treatments. Control theory might be an effective approach to this end, as proven by the long-established application to therapy design and testing. In this respect, we here introduce the Control Theory for Therapy Design (CT4TD) framework, which employs optimal control theory on patient-specific pharmacokinetics (PK) and pharmacodynamics (PD) models, to deliver optimised therapeutic strategies. The definition of personalized PK/PD models allows to explicitly consider the physiological heterogeneity of individuals and to adapt the therapy accordingly, as opposed to standard clinical practices.} CT4TD can be used in two distinct scenarios. At the time of the diagnosis, met{} allows to set optimised personalised administration strategies, aimed at reaching selected target drug concentrations, while minimizing the costs in terms of toxicity and adverse effects. Moreover, if longitudinal data on patients under treatment are available, our approach allows to adjust the ongoing therapy, by relying on simplified models of cancer population dynamics, with the goal of minimising or controlling the tumour burden. CT4TD is highly scalable, as it employs the efficient dCRAB (RedCRAB} optimization algorithm, and the results are robust, as proven by extensive tests on synthetic data. Furthermore, the theoretical framework is general, and it might be applied to any therapy for which a PK/PD model can be estimated, and for any kind of administration and cost. } As a proof of principle, we present the application of CT4TD to Imatinib administration in Chronic Myeloid Leukaemia, in which we adopt a simplified model of cancer population dynamics. In particular, we show that the optimised therapeutic strategies are diversified among patients, and display improvements with respect to the current standard regime.
机译:目前癌症研究中的关键挑战之一是在确定成功个性化治疗方面支持临床医生的计算策略的发展。控制理论可能是对此目的有效的方法,经过长期熟悉的申请来治疗设计和测试。在这方面,我们在这里介绍了治疗设计(CT4TD)框架的控制理论,它采用了患者特异性药代动力学(PK)和药效学(PD)模型的最佳控制理论,以提供优化的治疗策略。个性化PK / PD模型的定义允许明确地考虑个体的生理异质性并相应地适应治疗,而不是标准临床实践。} CT4TD可以用于两个不同的场景。在诊断时,遇到{}允许设定优化的个性化管理策略,旨在达到选定的目标药物浓度,同时最小化毒性和不良反应的成本。此外,如果可获得治疗患者的纵向数据,我们的方法可以通过依靠癌症种群动态的简化模型来调整正在进行的疗法,其目的是最小化或控制肿瘤负担。 CT4TD是高度可扩展的,因为它采用了高效的dcrab(Redcrab}优化算法,并且结果是强大的,因此通过对合成数据的广泛测试证明。此外,理论框架是通用的,并且可能适用于任何治疗可以估计PK / PD模型,以及任何类型的管理和成本。}作为原则证明,我们介绍了CT4TD在慢性骨髓白血病中的伊马替尼给药,其中我们采用了一种简化的癌症种群动态模型。特别是,我们表明,优化的治疗策略在患者中多样化,并对当前标准制度展示改进。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号