✦ LIBER ✦

Intracellular Accumulation and Mechanism of Action of Doxorubicin in a Spatio-temporal Tumor Model

✍ Scribed by TRACHETTE L. JACKSON

Publisher: Elsevier Science
Year: 2003
Tongue: English
Weight: 560 KB
Volume: 220
Category: Article
ISSN: 0022-5193
DOI: 10.1006/jtbi.2003.3156

No coin nor oath required. For personal study only.

✦ Synopsis

A spatio-temporal model of tumor response to sequestered, intracellular doxorubicin is presented and simulated. An important feature of the model is the characterization of different mechanisms by which doxorubicin initiates the cell death cascade. The model predicts that the long-term response of the tumor to repeated rounds of therapy is very sensitive to changes in the threshold level of doxorubicin required to initiate apoptosis at the maximum rate. In fact, perturbations of this parameter mediate the difference between effective tumor regression and minimal growth delays. The model is also used to investigate which parameters are most influential in rendering the tumor drug resistant. Sensitivity analysis shows that decreasing cellular permeability, as opposed to decreasing sequestration rate or increasing cellular efflux, is the most effective way for tumor cells to overcome the growth control afforded by successive rounds of treatment.

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