Spatio-temporal tumour model for analysis and mechanism of action of intracellular drug accumulation

Abstract

We have developed a one-dimensional tumour simulator to describe the biodistribution of chemotherapeutic drugs to a tumoral lesion and the tumour cell's response to therapy. A three-compartment model is used for drug dynamics within the tumour. The first compartment represents the extracellular space in which cells move, the second corresponds to the intracellular fluid space (including cell membrane) which is in direct equilibrium with the extracellular space, and the third is a non-exchangeable compartment that represents sequestered drug which is trapped in the nucleus to damage the cellular DNA,directly triggering cell death. Analytical and numerical techniques (Finite Element Method) are used to describe the tumour's response to therapy and the effect of parameter variation on the drug concentration profiles in the three compartments.

Understanding the effect of measurement time on drug characterization

“…While some of these models assume spherical tumors, the models largely neglect detailed spatial structure [69] and tumor cell heterogeneity [70]. Our models are also not detailed enough to accurately capture the mechanisms of action of many chemotherapy agents [71]. These limitations are likely the reason there is discrepancy between our findings and experimental measurements [13][14][15][16][17].…”