Mathematical and computational models of drug transport in tumours
Mathematical and computational models of drug transport in tumours
复制标题
DOI：
10.1098/rsif.2013.1173
复制
发表时间：
2014-05-06
影响因子：
3.9
通讯作者：
Phillips, R. M.
中科院分区：
文献类型：
--
作者：
Groh, C. M.;Hubbard, M. E.;Phillips, R. M.
预测药物在其药代动力学（PK）寿命内渗透到肿瘤微环境中的程度的能力将提供有关治疗反应的有价值的信息。由于PK特征与给药途径和时间表直接相关，因此可以预测药物给药时间表的计算机模拟工具将简化临床试验设计，从而使药物最佳递送至肿瘤。本文探讨了数学和计算建模技术的应用，以帮助提高我们对药物输送的基本机制的理解，并比较了一个简单的模型与更复杂的方法的性能。开发了三种药物转运模型，均基于相同的药物结合模型，并通过定制的体外实验进行参数化。他们的预测，比较“肿瘤索”的几何形状，定性和定量相似。我们评估了改变所供应药物的PK特征以及药物与肿瘤细胞的结合亲和力对到达细胞的药物浓度和细胞在离供应血管任意距离处对药物的累积暴露的影响。这是对开发一个有用的药物转运建模工具的贡献，告知策略的肿瘤细胞的治疗是“药代动力学耐药”化疗策略。
The ability to predict how far a drug will penetrate into the tumour micro-environment within its pharmacokinetic (PK) lifespan would provide valuable information about therapeutic response. As the PK profile is directly related to the route and schedule of drug administration, an in silico tool that can predict the drug administration schedule that results in optimal drug delivery to tumours would streamline clinical trial design. This paper investigates the application of mathematical and computational modelling techniques to help improve our understanding of the fundamental mechanisms underlying drug delivery, and compares the performance of a simple model with more complex approaches. Three models of drug transport are developed, all based on the same drug binding model and parametrized by bespoke in vitro experiments. Their predictions, compared for a 'tumour cord' geometry, are qualitatively and quantitatively similar. We assess the effect of varying the PK profile of the supplied drug, and the binding affinity of the drug to tumour cells, on the concentration of drug reaching cells and the accumulated exposure of cells to drug at arbitrary distances from a supplying blood vessel. This is a contribution towards developing a useful drug transport modelling tool for informing strategies for the treatment of tumour cells which are 'pharmacokinetically resistant' to chemotherapeutic strategies.