Table 2.
Summary of some recent studies exploring novel treatment options for cisplatin-resistant testicular germ cell tumors.
| Drug | Main Mechanism/Drug Class | Main Findings | Reference |
|---|---|---|---|
| Cabazitaxel | Chemotherapy; Taxane (microtubule inhibitor) | Clinical study. Limited activity in heavily treated refractory GCTs. | [195] |
| Dissulfiram | ALDH inhibitor (cancer stem cell marker) | Pre-clinical study. Synergistic antitumor effect (+ cisplatin) in an in vivo model. Restores sensitivity to cisplatin. | [42] |
| Everolimus | mTOR inhibitor | Clinical study. Limited activity in heavily treated refractory GCTs. | [194] |
| Sunitinib | RTK inhibitor (including VEGFR) | Pre-clinical study. Antitumor effect (including a reduced vasculature) in an in vivo model, including of a cisplatin resistant disease. | [199] |
| Avelumab | Immunotherapy; PD-L1 inhibitor | Clinical study. Well-tolerated but limited activity in heavily treated refractory GCTs. | [180] |
| Pembrolizumab | Immunotherapy; PD-1 inhibitor | Clinical study. Well-tolerated but limited activity in heavily treated refractory GCTs. | [178] |
| Durvalumab and Tremelimumab | Immunotherapy; anti-PD-L1 and anti-CTLA4 | Clinical study. Partial response and stable disease in 2 patients; remaining with disease progression. | [179] |
| 5-azacytidine | Epigenetics; Demethylating agent (nucleoside analog) | Pre-clinical study. Proapoptotic effect at low nM concentrations and overcomes cisplatin resistance. | [184] |
| Decitabine | Epigenetics; Demethylating agent (nucleoside analog) | Pre-clinical study. Causes DNA damage, promotes p53 and p21 activation, downregulates pluripotency factors, and activates ATM. Restores sensitivity to cisplatin. | [129,131] |
| Guadecitabine | Epigenetics; Demethylating agent (nucleoside analog) | Pre-clinical study. Restores sensitivity to cisplatin in in vivo models. | [185] |
| JQ1 | Epigenetics; BET inhibitor | Pre-clinical study. Induces apoptosis, more prominent in resistant clones compared to parental. | [191] |
| C63 and BRD-K98645985 | Epigenetics; ARID1A (chromatin remodeler) inhibitor | Pre-clinical study. ARID1A inhibitors sensitizes cisplatin-resistant cells to ATR inhibition. | [192] |
| Romidepsin | Epigenetics; HDAC inhibitor | Pre-clinical study. Antitumor effect, including in cisplatin-resistant cells. | [190] |
| Olaparib | DNA repair; PARP inhibitor | Pre-clinical study. Antitumor effect as monotherapy and sensitization to cisplatin. | [92] |
Abbreviations: GCT: germ cell tumor, HDAC: histone deacetylase, mTOR: mammalian target of rapamycin, PARP: poly (ADP-ribose) polymerase, RTK: receptor tyrosine kinase, and VEGFR: vascular endothelial growth factor receptor.