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Because of our increasing understanding of the mechanisms relevant to the genesis of cancer, we are experiencing a transition from disease to target-oriented therapy.The new concepts, however, bring major problems regarding the set-up of early clinical trials.On one hand, there is limited availability of predictive in vitro models and on the other hand, there is the need to perform early clinical trials in heavily pretreated patients with a considerable tumor load.Maximum tolerated dose (MTD) and response rate, however, are no longer the only decision-making endpoints of phase Ⅰ/Ⅱ trials.Therefore, endpoints different from those we are experienced to use for cytotoxic drugs need to be developed.Biomarkers represent a chance to allow proof of principle in early clinical trials in order to move rapidly to phase Ⅲ and registration.Potential biomarkers can be based on biopsy material, functional imaging or proteomic approaches dependent from the kind of drug under development.They can help to define subpopulations of patients who profit or do not profit from therapy.Proteomics has shown to be a potential tool to discriminate between benign and malignant tumor lesions.This technique also holds promise for the monitoring of functional effects of investigational agents and is expected to provide us with new biomarkers for evaluation of response and/or resistance.In colorectal carcinoma expression of the epidermal growth factor receptor (EGFR) is associated with a more aggressive clinical course and represents a promising molecular target for cancer therapy.Gefitinib selectively inhibits the EGFR tyrosine kinase activity and has demonstrated antiproliferative effects in colorectal carcinoma.