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Stochastic modeling of carcinogenesis: State space models and estimation of parameters
Unraveling the complexity of cell cycle effects of anticancer drugs in cell populations
1.  Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea, 62, 20157 Milano, Italy 
The model adopted for data analysis and interpretation is the result of merging two models, one for the cell cycle and the other for the drug effects. The first exploits the results of the theory of agestructured cell population dynamics while the second is based on distinct parameters ("effect descriptors") directly linked to cell cycle arrest, damage repair or cell death in $G_1$ and $G_2M$ and to inhibition of DNA synthesis and death in $S$. The set of values of the effect descriptors which are coherent with all experimental data are used to estimate the cytostatic and cytotoxic effects separately.
Applying the procedure to data from in vitro experiments, we found complex but biologically consistent patterns of time and dose dependence for each cell cycle effect descriptor, opening the way for a link to the parallel changes in the molecular pathways associated with each effect.
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