Table 2.
Synthetic lethal interactions and chemical tools for the targeted therapy of SWI/SNF-mutant cancers.
| SWI/SNF-deficiency | Synthetic lethal interaction/ epigenetic antagonism | Inhibitors | Ref. |
|---|---|---|---|
| SMARCA4 | SMARCA2 | PFI-3#, ACBI1#, ATPase-14# | [6, 65, 66] |
| ACTB | n/a | [5] | |
| ARID2 | n/a | [5] | |
| CDK4/6 | Palbociclib§, Abemaciclib§, Ribociclib§ | [10, 111] | |
| Aurora A | Tozasertib* (VX-680) | [9] | |
| OxPhos | IACS-010759* | [134] | |
| BET | ( + )-JQ1#, OTX-015* | [135] | |
| EZH2 | Tazemetostat§, GSK126*, CPI-169# | [136–138] | |
| ARID1A | ARID1B | n/a | [7, 64] |
| EZH2 | GSK126* | [136, 139] | |
| PARP | Talazoparib§, Olaparib§, Rucaparib§, Veliparib§ | [119, 120] | |
| PI3K/AKT | MK-2206*, Perifosine*, Buparlisib* | [49] | |
| ATR | VE-821#, VX-970 (M6620)* | [98] | |
| Abl, Src, c-KIT | Dasatinib§ | [110] | |
| GCLC | Buthionine sulfoximine* | [128] | |
| Aurora A | TCS-7010# | [108] | |
| HDAC6 | Ricolinostat (ACY-1215)* | [114] | |
| SMARCC1 | SMARCC2 | n/a | [5] |
| SMARCA2 | SMARCA4 | dBRD9# | [140] |
| PBRM1 | EZH2 | GSK126* | [136, 141] |
| ARID2 | PARP | Veliparib§ | [56] |
| SMARCB1 | EZH2 | Tazemetostat§ | [29] |
| HDAC | Panobinostat§ | [112] | |
| BRD9 | BI-7273#/9564#, dBRD9#, VZ185# | [21, 27] | |
| MDM2/4 | Idasanutlin* | [121] | |
| UBE2C | Ixazomib§, bortezomib§ | [123] | |
| SS18-SSX | BRD9 | dBRD9# | [27, 28] |
| KDM2B | n/a | [124] | |
| ATR | VX-970*, AZD6738* | [142] |
#Chemical probe. *Clinical probe. §FDA-approved drug.