This thesis focuses on targeted anticancer agents. An important class of these agents are the tyrosine kinase inhibitors (TKIs). One of the first steps in TKI treatment development is defining... Show moreThis thesis focuses on targeted anticancer agents. An important class of these agents are the tyrosine kinase inhibitors (TKIs). One of the first steps in TKI treatment development is defining whether a specific type of cancer, for example the sarcomas in chapter 3 of this thesis, express the receptors that are targeted. Once a TKI is developed, phase I studies are conducted to characterize the safety and side effects of the drug when administered to patients. When relevant side effects emerge, studies investigating the underlying mechanisms leading to these side effects are called for. Also pharmacogenetic studies can be performed to investigate whether certain heritable genetic variations influence efficacy or safety of the drug. After the phase I studies have proven the drug to be safe, the drug can be further developed. This includes the investigation of the TKI when combined with other anticancer agents. Items of all the described steps in TKI development are described in this thesis. Show less
