Table 1.

The parameters of the model and the values that were used

ParameterValuesDescription
Dominant loci0-6 loci (3 for therapy experiments)A mutation in either allele of these loci reduces the average cell cycle time of the cell by one-time step.
Recessive loci1-6 loci (2 for therapy experiments)Both alleles of these loci must be mutated to reduce the average cell cycle time by one-time step.
Mutator loci1 locusNo. of loci that when mutated increase the mutation rate of the cell.
Mutation rate10−5, 4 × 10−6, 2 × 10−6, 10−6The base mutation rate of the cells per locus per cell division.
Mutator factor10 or 100 (100 in experiments)Increase in the mutation rate for cells with mutator mutations (1 or 2 orders of magnitude).
Reversible mutationsYes/noWhether a mutant phenotype can be rescued by further mutations.
Time of chemotherapy8,000, 16,000, or 24,000 time stepsThe time step at which the cytotoxic therapy starts (∼11, 22, and 33 years after initiation).
Follow-up time3,600 time steps5 years of follow-up after therapy to test the efficacy of the simulated treatment.
No. of drugs (no. of drug resistance loci)1-6 drugs (loci)No. of cytotoxic drugs requiring independent mutations for resistance. There is one resistance locus per drug.
Chemotherapy durationOne-time stepCytotoxic therapies are applied in a single time step.
Chemotherapy efficacy1The probability a sensitive cell dies in one-time step in the presence of cytotoxins.
Time of benign booster8,000, 16,000, or 24,000 time stepsTime at which the benign booster treatment begins.
Benign booster duration3,600 time stepsThe benign boosters are applied over the entire duration of the follow-up (5 years).
Benign target locusDominant, recessive, mutator, drug resistanceThe locus used by the benign cell booster to distinguish benign (wild-type at locus) from nonbenign (mutated at locus) cells.
No. of cells in the neoplasm4,096 cellsThe simulated neoplasm consists of 4,096 cells in a 64 × 64 cell grid on the surface of a simulated tube.
  • NOTE: The model can simulate a variety of assumptions about the nature of progression and dysplasia.