Table 2.
An overview of drugs, drug-like compounds, and chemical compounds tested on ATRT cell lines, animal models, and clinical trials*
| Target/Mode of Action/Class | Phase of testing at which found to be effective or used | Refs | ||
|---|---|---|---|---|
| Preclinical Studies | Early Phase Clinical Trials | |||
| Classic Chemotherapy and DNA Damaging Agents | Alkylating agents | Carmustine,† thiotepa,† ifosfamide† | Carmustine, ifosfamide, temozolomide (nct00946335, nct01076530) | 14,31, 54–59 |
| Antimetabolite | Intraventricular methotrexate (NCT01737671, NCT02684071) | 60 | ||
| Guanosine analogs | Ribavarin†‡ | 61 | ||
| Intercalating agents | Actinomycin D,† idarubicin,† mitoxantrone,† doxorubicin†‡ | 51,54, 62 | ||
| Platinum compounds | Oxaliplatin† | Oxaliplatin (NCT00047177) | 54,63, 64 | |
| Topoisomerase inhibitors | Irinotecan,† etoposide† | Irinotecan (NCT00138216), Etoposide (NCT00392886) | 62,65, 66 | |
| Vinca alkaloid | Vinorelbine,† vincristine†‡ | 51,54 | ||
| Kinase Inhibitors | AKT | MK-2206† | 67 | |
| ALK, TGFbeta | SB431542† | 68 | ||
| Aurora A | Alisertib (MLN8237)† | Alisertib (NCT02114229) | 69–72 | |
| EGFR-HER2 | Lapatinib*†‡ | 73 | ||
| IGF-1R | NVP-AEW451† | 67 | ||
| MEK | Selumetinib† | 74 | ||
| mTOR | Rapamycin*† | Rapamycin* (NCT03387020, NCT01331135) | 54 | |
| mTORC1/2 | TAK228 (sapanisertib)†‡ | 75 | ||
| Multi-TKI | Dasatinib,*†‡ imatinib,*† kw-2449,† nilotinib*,† r-1530,*† sorafenib,*† sunitinib,*† lenvatinib*†‡ | 18,51, 54,65, 72,76 | ||
| PDGFR/FGFR | Ponatinib*† | 77 | ||
| PLK1 | Volasertib (BI6727)*†‡ | 78 | ||
| PLK4 | CFI-400945,†‡ CFI-400437,† centrinone,† centrinone-B† | 72,79, 80 | ||
| PTK7 | Vatalanib† | 81 | ||
| VEGF | Axitinib,*† cabozantinib,*†‡ pazopanib,*†‡ | Cediranib (NCT00326664) | 4,72 | |
| Cell Cycle Targets | CDK2 inhibitors | Roscovitine† | 54 | |
| CDK4/6 inhibitors | Palbociclib*†‡ | Ribociclib* (NCT03387020), Abemaciclib* (NCT02644460) | 49,82 | |
| Epigenetic Targeting Compounds | Bromo/BET | JQ1†‡ | 18,83, 84 | |
| BRD9 | BI-9564,† I-BRD9† | 85 | ||
| Demethylating agent | 5-AZA-2′-deoxycytidine (decitabine)*† | 62 | ||
| EZH2 | 3-Deazaneplanocin A (DZNep),† UNC1999,† tazemetostat*†‡ | Tazemetostat* (NCT02601937, NCT02875548, NCT02601950), Pediatric MATCH (NCT03213665) | 18,62, 86,87 | |
| G9a lysine methyltransferase | UNC0638† | 18 | ||
| Histone deacetylase inhibitors (HDACi) | LAQ824 (Dacinostat),† vorinostat (SAHA),*† valproic acid,*† SNDX-275 (entinostat),*† trichostatin A*† | Vorinostat* (SAHA), (NCT01076530, NCT00217412), valproic acid* | 18,62, 88–92 | |
| Pathway/Lineage Specific Compounds | BMP | Dorsomorphin*† | 18 | |
| Notch | DAPT*† | RO4929097 (NCT01088763) | 18 | |
| WNT inhibitor | Casin,*† niclosamide,† pyrvinium,† WNT-c59† | 93 | ||
| Antibody | 131-I-labeled monoclonal Ab: 8H9 (NCT00089245), 3F8 (NCT00445965) | |||
| Ornithine decarboxylase | DFMO (NCT03581240) | |||
| Oncolytic virus | Measles virus (MV)*†‡ | Modified measles virus (MV-NIS, NCT02962167) | 94 | |
| Other compounds | ALDH inhibitor | Disulfiram*†‡ | 55 | |
| LOX inhibitor | BAPN†‡ | 95 | ||
| Diferuoylmethane | Curcumin*† | 54 | ||
| Flavonoid | Apigenin*† | 54 | ||
| PPARg agonist | Ciglitazone† | 54 | ||
| Exosome release inhibitor | GW4869† | 96 | ||
| MDM2, MDM4, MDMX | Idasanutlin,*† ATSP-7041† | ALRN-6924 (NCT03654716) | 97 |
*In vitro and in vivo studies are denoted with a dagger (†) or double dagger (‡), respectively. Agents without FDA approval are denoted with an asterisk (*). FDA approved targeted agents with preclinical or clinical data suggesting favorable blood‒brain barrier penetration are bolded. Many of agents are FDA approved, and therefore with further preclinical testing (namely in vivo testing on transgenic mouse models and/or xenografts) may be promising agents to quickly translate into clinical use. Citations include only compounds deemed by the authors to be effective in their study.