Combination_Cyto_and_Apop_MutB.xlsx

Results of simulating combination drug chemotherapy of a multidrug resistant cancer mutant in an agent-based computer model of cell dynamics in human colon crypts. The drugs were the cytotoxic 5-flurouracil, and the apoptotic sulindac. The cancer cells (MutB) had a 1.08X probability of dividing, and 1.05X the probability of dying, of normal cells at the same position in the colon crypt. The cancer cells were resistant and continued to proliferate, when treated with each single drug separately. Combination chemotherapy with the two drugs was initiated when 50% of the cells in the crypt were cancer cells. There are 2430 drug combination dose schedules that cured all cancer cells in each of 50 simulation runs, and retained crypt function. Each dose schedule included the following: Column A, Duration of the cytotoxic treatment in computer steps (one step is equivalent to 4 hrs); Column B, Interval between cytotoxic doses in computer steps; Column C, Lethality of cytotoxic dose, a factor that increases the probability that a cell will die above that determined by the cell’s position in the crypt; Column D, Duration of apoptotic treatment; Column E, Interval between apoptotic doses; Column F, apoptotic treatment, a parameter that changes the size of the colon crypt by inducing apoptosis at the top of the crypt. This is intended as a supplement to a publication describing combination chemotherapy of multidrug resistant early-stage colon cancer.