DETERMINABILITY OF MODEL PARAMETERS IN A 2-STAGE DETERMINISTIC CANCERMODEL

We investigate the determinability of model parameters for a two-stage cancer model, using as an example chemically induced skin cancer in m ice. When the time course of the papilloma number and cancer rate are known, the rate of creation of initiated cells and their net-growth ra te can be uniquely determined. These two high-level parameters are suf ficient to uniquely simulate the experimental papilloma data. However, the mitotic and death rates of initiated and transformed cells cannot be determined from the available experimental data. The rate of creat ion of transformed cells and their net-growth rate cannot be determine d independently. Thus, although the deterministic two-stage cancer mod el can simulate the kinetics of papilloma formation and skin cancer da ta, many of the basic underlying biological parameters (i.e., mitotic and death rates) cannot be uniquely determined from the usually availa ble biological data. Published by Elsevier Science Inc.