Data from: Drug delivery in a tumour cord model: a computational simulation

The tumour vasculature and microenvironment is complex and heterogeneous, contributing to reduced delivery of cancer drugs to the tumour. We have developed an in silico model of drug transport in a tumour cord to explore the effect of different drug regimes over a 72h period and how changes in pharmacokinetic parameters affect tumour exposure to the cytotoxic drug doxorubicin. We used the model to describe the radial and axial distribution of drug in the tumour cord as a function of changes in transport rate across the cell membrane, blood vessel and intercellular permeability, flow rate, and the binding and unbinding ratio of drug within the cancer cells. We explored how changes in these parameters may affect cellular exposure to drug. The model demonstrates the extent to which distance from the supplying vessel influences drug levels and the effect of dosing schedule in relation to saturation of drug binding sites. It also shows the likely impact on drug distribution of the aberrant vasculature seen within tumours. The model can be adapted for other drugs and extended to include other parameters. The analysis confirms that computational models can play a role in understanding novel cancer therapies to optimise drug administration and delivery.肿瘤脉管系统与肿瘤微环境结构复杂且异质性显著，这会降低抗癌药物向肿瘤部位的递送效率。我们构建了肿瘤索内药物转运的计算机模拟（in silico）模型，旨在探究72小时观测周期内不同给药方案的作用效果，以及药代动力学参数的变化如何影响肿瘤对细胞毒性药物多柔比星（doxorubicin）的暴露水平。我们借助该模型刻画了肿瘤索内药物的径向与轴向分布特征，该分布随跨细胞膜、血管及细胞间的转运速率、流体流速、癌细胞内药物结合与解离比率的改变而变化，并探究了上述参数的调整如何影响细胞对药物的暴露情况。该模型阐明了肿瘤供养血管的距离对药物浓度的影响程度，以及给药方案与药物结合位点饱和之间的关联；同时揭示了肿瘤内异常脉管系统对药物分布的潜在影响。本模型可适配其他药物，并可扩展纳入更多研究参数。本分析证实，计算模型可在解析新型癌症疗法、优化药物给药与递送方案方面发挥重要作用。