Skip to main content

Table 1 Pre-clinical studies of EZH2 inhibitors in MM

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
  1. aNote: OR-S2 and UNC1999 are dual EZH1/2 inhibitors