Mutant cell dynamics and drug resistance development


Most cancers are caused by either a single or more often an accumulation of mutations and there- by altered cell differentiation properties. Nowadays many of these mutations are known and in individual cases molecular targeted drugs were developed, converting ultimate life threatening into chronic diseases. Unfortunately cancer cells tend to develop resistance, leading to treatment failures. We analyzed a resistance inducing experiment by applying a minimalistic mathematical model and are able to infer important system parameters, highlighting different mechanisms causing resistance. However translating these in vitro results into an in vivo dynamics is chal- lenging, due to complex cell interactions in hierarchical organized tissues. Yet another individual based mathematical model allows us to describe basic properties of mutant cell dynamics in such tissues. Most important the compartment of the mutants origin and the time development of the mutant population can be inferred. From this it is apparent that small differences in vitro can lead to important consequences in vivo.