Germ cell tumors of the gonads: a selective review emphasizing problems in drug resistance and current therapy...

Germ cell tumors are the most common malignancies in men under 50 years and also the most common cause of death from solid tumors in this age group. The past few decades have seen no change in the fact that 40% of such tumors have already metastasized by the time of initial diagnosis. In contrast to the majority of metastasized solid tumors, germ cell tumors can be effectively treated by cisplatin-based polychemotherapy. They only rarely show resistance mechanisms. Resistance to chemotherapeutics has been extensively examined in urological and nonurological tumors. Various mechanisms enabling malignant tumor cells to avoid the cytotoxic effect of chemotherapeutics have been discovered in the past few years. On the other hand, the reasons for the excellent responsiveness of germ cell tumors to chemotherapy have remained unclear. Theoretical models for the high cure rates of germ cell tumors after cisplatin-based polychemotherapy consider, on the one hand, molecular-biological aspects of malignant germ cell tumor cells per se and, on the other hand, the immunological and nonimmunological response mechanisms of the patients. This review article summarizes theoretical models for the high chemotherapy sensitivity of germ cell tumors and points out new therapeutic prospects.