Resistancy and/or progression – Failure or only a short stop

Nowadays, with the continuously in creasing demand for targeted diagnostics and therapy, we are approaching an ideal stage when the most effective treat ment for a given patient could be selected. However, some basic problems are still waiting to be solved. One major hurdle is the heterogeneity, the formation of subclones with different signifi cance during progression, but with the capacity to overgrow after the failure of the initial therapy. The importance of this phenomenon is refl ected in the daily practice where targeted therapy is allowed to treat only locally extended or metastatizing tumors. Therefore, it is not as to nishing, that the clinical success is usually temporary, the disease in spite of the good response at the beginning will progress. The main reason is the resistancy against the carefully analysed and applied therapeutic drugs, which has several options (e.g. new mutations, crosstalks between pathways, faults of feed-backs, etc.). This review focuses on the acquired resistancy with some relevant examples. Among the open questions we can recall e.g. the resistancy in combination therapy, or the suggested link between resistancy and progression including the potential use of drug rechallenge.