Table 2. Potential targets in ARID1A-mutated tumors in preclinical studies.
| Pathway | Target | Drug class | Drugs investigated | Ref. |
|---|---|---|---|---|
| Epigenetic | HDAC2 | HDAC inhibitor | Vorinostat | (102) |
| HDAC6 | HDAC inhibitor | Ricolinostat (ACY1215) | (103) | |
| BRD2 | BET inhibitor | iBET-762 | (104) | |
| HDAC1, BRD4 | BET inhibitor (BRD4-i) | Pexidartinib (PLX2853) | (34) | |
| ARID1B | ARID1B knockout | Non targetable in vivo | (105) | |
| PIK3IP1 | EZH2 inhibitor | Tazemetostat | (106,107) | |
| PI3K/AKT/mTOR | PI3K | PI3K-inhibitor | Buparlisib | (100,106) |
| AKT | AKT-inhibitor | Perifosine, MK-2206 | (100) | |
| mTOR | mTORC1/2 inhibitor | AZD8055 (in OCCC, ARID1A-independent) | (108) | |
| mTOR + PI3K | Dual-PI3K-/mTOR-i | Dactolisib (BEZ235), DS-7423 | (109,110) | |
| Cell cycle | YES1 (SRC family) | Tyrosine kinase inhibitor | Dasatinib | (99,111,112) |
| Genomic instability | TOP2A | ATR inhibitor | Berzosertib (VX-970) | (113) |
| PARP | PARP inhibitor | Olaparib, Rucaparib, Veliparib, Talazoparib (BMN673) | (114) | |
| Inflammatory | IL-6/IL-6-receptor | Anti-IL-6 agents | Tocilizumab (anti-IL-6-receptor ab), Siltuximab (anti-IL-6 ab) | (115) |
| Metabolic inhibition | Increase of ROS | GSH inhibitor GCLC inhibition |
APR-246 buthionine sulfoximine |
(116) |
| Immune modulation | PD-1 | PD-1 inhibitor | Pembrolizumab, Nivolumab | (117) |
| MMR/MSH2 deficiency | (118) |