Mathematical models of the steps involved in the systemic delivery of a chemotherapeutic to a solid tumor: From circulation to survival.
Mathematical models of the steps involved in the systemic delivery of a chemotherapeutic to a solid tumor: From circulation to survival.
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DOI：
10.1016/j.jconrel.2015.06.026
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发表时间：
2015-08-28
期刊：
影响因子：
--
通讯作者：
Searson PC
中科院分区：
文献类型：
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作者：
Ulmschneider MB;Searson PC
静脉给药化疗治疗实体瘤的疗效取决于一系列步骤，包括循环、通过增强渗透性和滞留效应而外渗、肿瘤微环境中的运输、细胞摄取和运输机制以及药物作用机制。这些步骤是耦合的，因为循环中的时间依赖性浓度决定了肿瘤微环境中的浓度和分布，从而决定了肿瘤内单个细胞的摄入量。尽管预测能力仍然有限，但已经为交付过程中的每个步骤开发了模型。我们对给药过程中各个步骤的理解的进步将导致预测能力提高的精确模型，并最终允许开发将药物的系统给药与生存概率联系起来的综合模型。基于患者具体数据预测结果的综合模型可用于选择最佳治疗方案。在这里，我们概述了交付过程中各个步骤的当前模型，并强调了开发集成模型的关键知识差距。
The efficacy of an intravenously administered chemotherapeutic for treatment of a solid tumor is dependent on a sequence of steps, including circulation, extravasation by the enhanced permeability and retention effect, transport in the tumor microenvironment, the mechanism of cellular uptake and trafficking, and the mechanism of drug action. These steps are coupled since the time dependent concentration in circulation determines the concentration and distribution in the tumor microenvironment, and hence the amount taken up by individual cells within the tumor. Models have been developed for each of the steps in the delivery process although their predictive power remains limited. Advances in our understanding of the steps in the delivery process will result in refined models with improvements in predictive power and ultimately allow the development of integrated models that link systemic administration of a drug to the probability of survival. Integrated models that predict outcomes based on patient specific data could be used to select the optimum therapeutic regimens. Here we provide an overview of current models for the steps in the delivery process and highlight knowledge gaps that are key to developing integrated models.