Table 2:
Overview of epigenetic drugs/inhibitors along with the structures implicated in SCLC.
| Drug/Inhibitor | Structure | Target | Outcomes | Reference |
|---|---|---|---|---|
| Iadademstat (GSK2879552/ORY-1001) |
|
LSD1 | -Activates NOTCH -Decreases ASCL1 |
[89, 131] |
| T-3775440 |
|
LSD1 | -Acts on LSD1-INSM1 interactions -Decreases ASCL1 |
[145, 265] |
| Vorinostat |
|
HDAC | -Increases acetylation of histone H3 -Enhances the efficacy of cisplatin & BCL2 inhibitors |
[195, 202, 203] |
| Belinostat |
|
HDAC | -Increases lysine acetylation -Effective in NE subtypes |
[195, 201] |
| Romidepsin |
|
HDAC | -Increases acetylation of histone H3 & H4 | [195, 266] |
| Panobinostat/LBH589 |
|
HDAC | -Increases efficacy of DNMT inhibitors -Sustains stable diseases |
[204, 267] |
| Trichostatin A |
|
HDAC | -Effective in EGFR mutated distinct subtype -Increases acetylation of histone H4 |
[200, 268] |
| Pracinostat |
|
HDAC | -Increases acetylation of histone 3 (H3K27ac) -Increases CDH1 expression -Effective in CREBBP deleted SCLC tumors |
[128] |
| Ricolinostat |
|
HDAC | -Enhances efficacy of BET inhibitors -Activates NK cell mediated innate immunity |
[207] |
| MGCD0103/Mocetinostat |
|
HDAC | -Increases efficacy of topoisomerase inhibitors -Increases tumor antigen presentation -Enhances check-point inhibitor therapy |
[205, 252] |
| Valproate/valproic acid |
|
HDAC | -Augments cisplatin and etoposide activity (standard first-line chemotherapy) | [206] |
| 5-AzaC |
|
-Modulates death receptor & caspase-8 expression | [253, 269] | |
| JQ1 |
|
BET | -Enhances efficacy of HDAC inhibitors -Activates NK cell mediated innate immunity |
[207] |
| EPZ011989 |
|
EZH2 | -Decreases methylation of histone H3 (H3K27me3) -Increases SLFN11 expression -Prevents emergence of chemoresistance -Augments chemoresponse |
[76, 270] |
| Tazemetostat/ EPZ-6438 |
|
EZH2 | [76] |