Essay Example on EZH2 inhibition for the treatment of hematological Cancers

Their drug termed MAK683 has been shown to markedly alter global gene expression in human lymphoma cell lines as well as induced pronounced tumor regression in human lymphoma subcutanoues grafts 34 However the Food and Drug Administration has granted fast track status to two of their trials indicating the high therapeutic potential of Tazemetostat Drug Mechanism Company Disorders Trial number Tazemetostat Competitive SET inhibitor Epizyme Inc Various Lymphomas NCT03028103 Diffuse B Cell Lymphoma NCT02875548 Various Lymphomas NCT03010982 Various Lymphomas NCT01897571 National Cancer Institute Non Hodgkin s Lymphoma NCT03217253 Various Lymphomas NCT03213665 MAK683 Inhibition of PRC2 family member EED Novartis Diffuse Large B cell Lymphoma NCT02900651 GSK2816126 Competitive SET inhibitor Glaxo Smith Kline Various Lymphomas NCT02082977 CPI 1205 Competitive SET inhibitor Constellation B cell Lymphoma NCT02395601 Table 1 Current clinical trials testing EZH2 inhibitors for treatment of hematological malignancies The question remains as to whether EZH2 inhibitors will truly transform the treatment of blood cancers In light of recent successes of immunotherapies like 

CAR T cells in treating leukemia the bar for transformative therapy in hematological cancer has been set high The long term worth of EZH2 inhibitors will likely rely on two key factors patient selection and cellular plasticity First it will be critical to determine which patients would respond well to EZH2 inhibition As Lund et al noted in their excellent review 15 EZH2 alterations are highly variable therefore only patients identified to have a causative EZH2 mutation or overexpression of EZH2 should be considered for treatment with these drugs Patients in which EZH2 activity may be limiting the aggression of cancer growth should never be given EZH2 inhibition Further not all patients referenced in genetic screens present with EZH2 mutations Morin et al discovered only 21 of diffuse B cell lymphoma patients were mutant carriers 35 further examples of adaptation in leukemia cells have also been noted 36 Epigenetic represent a key factor in how cells adapt gene expression to their changing environment Therefore I suspect that using drugs like EZH2 inhibitors that block histone modification could limit cellular adaptation In conclusion EZH2 inhibitors are an exciting facet of ongoing drug development for treating cancer Preclinical studies support the notion that these drugs can powerfully influence the progression of cancer The multitude of clinical trials underway for these drugs should be observed closely In patients found to have causative gain of function EZH2 mutations these drugs have great promise In the long run I believe that the true usefulness of EZH2 inhibitors will deal with their influence on epigenetics As research continues to better define the role of epigenetics in cancer onset progression and drug resistance drugs that block major players in gene expression regulation will be critical