Figure 2.

Pre-target, on-target, post-target, and off-target mechanisms involved in cisplatin resistance in (testicular) germ cell tumors. Most studies have focused on the on-target and post-target mechanisms (evidence: +++). Pre-target mechanisms are not thought to be major factors in the acquisition of cisplatin resistance in these tumors (evidence +/−). Other mechanisms are currently being explored, and related data is building up. A better understanding of these mechanisms underlies the development of specific effective therapies of cisplatin-resistant patients (italics). Notice that epigenetic (de)regulation can be found within any type of mechanism. See text for details. Abbreviations: TLS: translesion synthesis, EMT: epithelial-to-mesenchymal transition, and TKIs: tyrosine kinase inhibitors.