Combination Chemotherapy of Multidrug-resistant Early-stage Colon Cancer: Determining Optimal Dose Schedules by High-performance Computer Simulation.

ABSTRACT: The goal of this project was to utilize mechanistic simulation to demonstrate a methodology that could determine drug combination dose schedules and dose intensities that would be most effective in eliminating multidrug resistant cancer cells in early-stage colon cancer. An agent-based model of cell dynamics in human colon crypts was calibrated using measurements of human biopsy specimens. Mutant cancer cells were simulated as cells that were resistant to each of two drugs when the drugs were used separately. The drugs, 5-flurouracil and sulindac, have different mechanisms of action. An artificial neural network was used to generate nearly two hundred thousand two-drug dose schedules. A high-performance computer simulated each dose schedule as a in silico clinical trial and evaluate

SUBMITTER: Cockrell C 

PROVIDER: S-EPMC9851383 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature