From: EZH2 as a therapeutic target for multiple myeloma and other haematological malignancies
Author (date) | EZH2 inhibitor | Model | Main findings | Ref. |
---|---|---|---|---|
Hernando et al. (2015) | E7438 (EPZ-6438) | MM cell lines | Cells become more adherent and less proliferative with EZH2 inhibition | [18] |
Mouse model | Slower progression of the tumor, with no effect on body weight | |||
Agarwal et al. (2016) | UNC1999a and GSK343 | MM cell lines and patient samples | Reduced viability in a dose and time-dependent manner via induction of apoptosis | [23] |
Zeng et al. (2017) | GSK126 | MM cell lines | Decreased proliferation and increased apoptosis, reduction in stem-cell like MM cells with EZH2 inhibition | [19] |
Mouse model | Slower progression of the tumor | |||
Pawlyn et al. (2017) | EPZ005687 and UNC1999a | MM cell lines and patient samples | EZH2 inhibition reduces MM cell viability by inducing cell cycle arrest and apoptosis | [21] |
Honma et al. (2017) | OR-S2a | MM cell lines | 6 out of 8 cell lines are hypersensitive to dual EZH1/2 inhibition | [33] |
Rizq et al. (2017) | UNC1999a | MM cell lines and patient samples | UNC1999 inhibited the growth of MM cell lines including resistant ones; cytotoxicity in MM patients cells, but not healthy donors; enhanced the cytotoxicity induced by bortezomib | [22] |
Mouse model | Reduced tumor growth; UNC1999 enhanced the cytotoxicity induced by bortezomib | |||
Alzrigat et al. (2017) | UNC1999a | MM cell lines and primary MM cells | Combining UNC1999 and BMI-1 inhibitor PTC-209 induces a significant reduction in cell viability compared to single agent | [34] |
Dimopoulos et al. (2018) | EPZ-6438 | MM cell lines resistant to IMiD | Combination of 5-Aza and EPZ-6438 could re-sensitize 7 of 8 cell lines to IMiD | [26] |
Rastgoo et al. (2018) | EPZ-6438 | MM cell lines and primary MM cells | EPZ-6438 reversed bortezomib resistance, combination with bortezomib revealed more pronounced effect on drug resistant cell lines | [17] |
Mouse model | Combination of bortezomib and EPZ-6438 significantly reduced the tumor size and prolonged the survival | |||
Combinations | ||||
 Neo et al. (2014) | GSK126 | MM cell line (MM1S) | The dose of GSK126 required for growth inhibition and death was reduced by the addition of PTX | [36] |
 Harding et al. (2018) | GSK126, EPZ-6438, UNC1999 | MM cell lines | Pre-treatment with EZH2 inhibitors sensitized cells to panobinostat regardless of sensitivity to single agent EZH2 inhibitor | [37] |
 Herviou et al. (2018) | EPZ-6438 | MM cell lines and primary MM cells | EPZ-6438 reduced the number of viable cells in 9/17 patients, without correlation with EZH2 expression. | [20] |
EPZ-6438 sensitized cells to lenalidomide and pre-treatment with EPZ-6438 could overcome lenalidomide resistance in resistant cell lines |