Curing metastatic cancer: lessons from testicular germ-cell tumours

Key Points Metastatic testicular germ-cell tumours (TGCTs), in contrast to nearly all other cancers in adults, can be cured with drugs (cisplatin-based combination chemotherapy). But why are metastatic TGCTs so curable? TGCT cells grown in the laboratory are 2–4 times more sensitive to cisplatin than most other types of cancer cell, so they provide a representative model system with which to study the mechanisms that control cisplatin sensitivity. Testis tumour cells are deficient in one particular type of DNA repair — nucleotide excision repair — and consequently have a reduced capacity to repair the DNA damage caused by cisplatin. Testis tumour cells are also defective in other aspects of DNA repair and are primed for apoptosis. Targeting DNA-repair proteins might sensitize other types of cancer to cisplatin. Most metastatic cancers are fatal. More than 80% of patients with metastatic testicular germ-cell tumours (TGCTs), however, can be cured using cisplatin-based combination chemotherapy. Why are TGCTs more sensitive to chemotherapeutics than most other tumour types? Answers to this question could lead to new treatments for metastatic cancers.