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Updated: Aug 6, 2026
Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional (3D) Model
Published on: June 11, 2014
Diffusivity and distribution of vinblastine in three-dimensional tumour tissue: experimental and mathematical
Szabolcs Modok1, Philip Hyde, Howard R Mellor
1Oxford Drug Resistance Group, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Headley Way Headington, Oxford OX3 9DU, UK.
Abstract:
The distribution of chemotherapeutics in solid tumours is poorly understood and the contribution it makes to treatment failure is unknown. Novel approaches are required to understand how the three-dimensional organisation of cancer cells in solid tumours affects drug availability. Since convective drug transport is limited by increased interstitial pressure in poorly vascularised cancers, the aim of this study was to measure the diffusive hindrance exerted by solid tumour tissue. Multicell layer tumour models comprising DLD1 colon cancer cells were characterised and fluxes were determined for [3H]-vinblastine and [14C]-sucrose. The mathematical models provided the diffusion coefficients for both compounds and predicted higher exposure of cells in the vicinity of vessels. The diffusion of vinblastine was three times slower than that of sucrose. Although slow diffusion delays vinblastine penetration into the avascular regions of tumours, the proliferating cells are generally in the marginal area of tumours. The mathematical model that we have developed enabled accurate quantification of drug pharmacokinetic behaviour, in particular, the diffusivity of vinblastine within solid tissue. This mathematical model may be adapted readily to incorporate the influence of factors mediating pharmacokinetic drug resistance.
Insights
Chemotherapy penetration in solid tumors is poorly understood. This study quantifies drug diffusion in tumor tissue, revealing vinblastine diffuses slowly, impacting treatment efficacy.
Area of Science:
- Oncology
- Pharmacology
- Biophysics
Background:
- Chemotherapeutic distribution within solid tumors significantly impacts treatment outcomes.
- Understanding drug penetration is crucial for overcoming treatment failure in cancer therapy.
- Interstitial pressure in poorly vascularized tumors limits convective drug transport.
Purpose of the Study:
- To quantify the diffusive hindrance of solid tumor tissue on chemotherapeutic agents.
- To investigate the impact of tumor architecture on drug availability.
- To develop a mathematical model for predicting drug pharmacokinetic behavior in tumors.
Main Methods:
- Utilized multicell layer tumor models with DLD1 colon cancer cells.
- Measured diffusion fluxes for [3H]-vinblastine and [14C]-sucrose.
- Employed mathematical modeling to determine diffusion coefficients and predict drug exposure.
Main Results:
- Developed a mathematical model to accurately quantify drug diffusion in solid tumor tissue.
- Vinblastine diffusion was found to be three times slower than sucrose diffusion.
- Predicted higher drug exposure for cancer cells located near tumor vasculature.
Conclusions:
- Slow diffusion of vinblastine may delay penetration into avascular tumor regions.
- The developed mathematical model accurately quantifies drug diffusivity within solid tissue.
- This model can be adapted to include factors contributing to pharmacokinetic drug resistance.
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