ABSTRAKT

Assays to predict the response of tumors towards chemotherapy are relevant for custom-tailored, individualized therapies. Clinically, chemotherapy is frequently hindered by drug resistance. Since most established cytostatic drugs lack sufficient tumor specificity, normal tissues are also affected by severe side effects. Novel strategies to broaden the narrow therapeutic range by separating the effective dose and toxic dose would be of great benefit for the patients. Whereas the statistical probability of therapeutic success is well-known for larger groups of patients from clinical therapy trials, it is, however, not possible to predict how an individual tumor will respond to therapy. Therefore, efforts have been undertaken to predict drug response in vitro. The idea is to determine sensitivity or resistance beforehand to subsequently choose the most effective clinical treatment for individual patients. This review provides an overview of our own experiences with predictive and prognostic markers for therapy response of tumors and survival time of patients from immunohistochemical detection to pharmacogenomic techniques. Markers identified in molecular biological approaches may not only serve for prediction of drug resistance of tumors and survival times of patients but may also as targets for novel treatment strategies. In the past, my co-investigators and I have studied chemical constituents of herbs used in traditional Chinese medicine. Our efforts have been focused on two target proteins, the multidrug resistance-conferring drug efflux transporter P-glycoprotein and the epidermal growth factor receptor (EGFR). Specific phytochemical inhibitors were identified for both target proteins. These small-molecule inhibitors may serve as adjuncts for future combination therapy regimens useful for managing individualized treatment for cancer patients.