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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Preclinical and Clinical Aspects of using Tazemetostate in Human Cancers

Author(s): Leila Mousazadeh, Behzad Mousazadeh, Jamshid Motaei, Faezeh Abbasi and Reza Jafarzadeh Esfehani*

Volume 28, Issue 16, 2022

Published on: 23 May, 2022

Page: [1329 - 1333] Pages: 5

DOI: 10.2174/1381612828666220408121514

Price: $65

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Abstract

Epigenetic drugs are novel drug categories with promising effects in different cancers. Tazemetostate is among the drugs that were recently used in clinical settings, especially in the treatment of specific tumors and lymphomas. There are a growing number of ongoing clinical trials evaluating the safety and efficacy of tazemetostate in different cancers. The present review addressed the available preclinical studies evaluating the combination of tazemetostate and other chemotherapy agents in treating different cancers and summarized the limited clinical evidence available regarding the efficacy of this novel Enhancer of Zeste Homolog 2 (EZH2) inhibitor in cancer. Based on the available clinical studies, tazemetostate could be considered a safe epigenetic agent with limited adverse events for treating specific types of lymphomas and solid tumors. However, the superiority of using tazemetostate over other chemotherapy agents in patients with cancer as well as using the drug for other clinical conditions, including non-alcoholic steatohepatitis, needs further investigation. Moreover, the effect of tazemetostate on human germline cells is clearly evaluated as some animal studies demonstrated that the drug can affect germline epigenome suggesting further studies on this issue.

Keywords: Tazemetostate, cancer, chemotherapy, epigenetics, pharmacology, solid tumor.

« Previous Next »
[1]
Dupont C, Armant DR, Brenner CA, Eds. Epigenetics: Definition, mechanisms and clinical perspective. Semin Reprod Med 2009; 27(5): 351-7.
[2]
Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev 2009; 23(7): 781-3.
[http://dx.doi.org/10.1101/gad.1787609] [PMID: 19339683]
[3]
Blackledge NP, Klose R. CpG island chromatin: A platform for gene regulation. Epigenetics 2011; 6(2): 147-52.
[http://dx.doi.org/10.4161/epi.6.2.13640] [PMID: 20935486]
[4]
Aghabozorgi AS, Sharif S, Jafarzadeh-Esfehani R, Vakili S, Abbaszadegan MR. Role of miRNA gene variants in the susceptibility and pharmacogenetics of colorectal cancer. Pharmacogenomics 2021; 22(5): 303-18.
[http://dx.doi.org/10.2217/pgs-2020-0159] [PMID: 33733820]
[5]
Sabeti Aghabozorgi A, Moradi Sarabi M, Jafarzadeh-Esfehani R, et al. Molecular determinants of response to 5-fluorouracil-based chemotherapy in colorectal cancer: The undisputable role of micro-ribonucleic acids. World J Gastrointest Oncol 2020; 12(9): 942-56.
[http://dx.doi.org/10.4251/wjgo.v12.i9.942] [PMID: 33005290]
[6]
Parizadeh SM, Jafarzadeh-Esfehani R, Ghandehari M, et al. Epigenetic drug therapy in the treatment of colorectal cancer. Curr Pharm Des 2018; 24(23): 2701-9.
[http://dx.doi.org/10.2174/1381612824666180730151904] [PMID: 30062956]
[7]
Aghabozorgi AS, Ebrahimi R, Bahiraee A, et al. The genetic factors associated with WNT signaling pathway in colorectal cancer. Life Sci 2020; 256: 118006.
[http://dx.doi.org/10.1016/j.lfs.2020.118006] [PMID: 32593708]
[8]
Parizadeh SM, Jafarzadeh-Esfehani R, Fazilat-Panah D, et al. The potential therapeutic and prognostic impacts of the c-MET/HGF signaling pathway in colorectal cancer. IUBMB Life 2019; 71(7): 802-11.
[http://dx.doi.org/10.1002/iub.2063] [PMID: 31116909]
[9]
Parizadeh SM, Jafarzadeh-Esfehani R, Hassanian SM, et al. Targeting cancer stem cells as therapeutic approach in the treatment of colorectal cancer. Int J Biochem Cell Biol 2019; 110: 75-83.
[http://dx.doi.org/10.1016/j.biocel.2019.02.010] [PMID: 30818083]
[10]
Huang H, Sabari BR, Garcia BA, Allis CD, Zhao Y. SnapShot: Histone modifications. Cell 2014; 159(2): 458.
[http://dx.doi.org/10.1016/j.cell.2014.09.037] [PMID: 25303536]
[11]
Kouzarides T. Chromatin modifications and their function. Cell 2007; 128(4): 693-705.
[http://dx.doi.org/10.1016/j.cell.2007.02.005] [PMID: 17320507]
[12]
Cruz C, Della Rosa M, Krueger C, et al. Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells. eLife 2018; 7: e34081.
[http://dx.doi.org/10.7554/eLife.34081] [PMID: 30274593]
[13]
Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D. Histone methyltransferase activity associated with a human multiprotein complex containing the enhancer of Zeste protein. Genes Dev 2002; 16(22): 2893-905.
[http://dx.doi.org/10.1101/gad.1035902] [PMID: 12435631]
[14]
Bruno M, Mahgoub M, Macfarlan TS. The arms race between KRAB–zinc finger proteins and endogenous retroelements and its impact on mammals. Annu Rev Genet 2019; 53(1): 393-416.
[http://dx.doi.org/10.1146/annurev-genet-112618-043717] [PMID: 31518518]
[15]
Cao R, Zhang Y. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol Cell 2004; 15(1): 57-67.
[http://dx.doi.org/10.1016/j.molcel.2004.06.020] [PMID: 15225548]
[16]
Batlevi CL. A closer look at tazemetostat. Clin Adv Hematol Oncol 2020; 18(12): 820-2.
[PMID: 33406058]
[17]
Hoy SM. Tazemetostat: First approval. Drugs 2020; 80(5): 513-21.
[http://dx.doi.org/10.1007/s40265-020-01288-x] [PMID: 32166598]
[18]
de Nigris F, Ruosi C, Napoli C. Clinical efficiency of epigenetic drugs therapy in bone malignancies. Bone 2021; 143: 115605.
[http://dx.doi.org/10.1016/j.bone.2020.115605] [PMID: 32829036]
[19]
Aury-Landas J, Girard N, Lhuissier E, et al. The antitumoral effect of the S-adenosylhomocysteine hydrolase inhibitor, 3-deazaneplanocin A, is independent of EZH2 but is correlated with EGFR downregulation in chondrosarcomas. Cell Physiol Biochem 2019; 53(4): 731-45.
[http://dx.doi.org/10.33594/000000168] [PMID: 31613064]
[20]
Wiese M, Schill F, Sturm D, et al. No significant cytotoxic effect of the EZH2 inhibitor tazemetostat (EPZ-6438) on pediatric glioma cells with wildtype histone 3 or mutated histone 3.3. Klin Padiatr 2016; 228(3): 113-7.
[http://dx.doi.org/10.1055/s-0042-105292] [PMID: 27135271]
[21]
Yang Q, Zhao S, Shi Z, et al. Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling. J Exp Clin Cancer Res 2021; 40(1): 120.
[http://dx.doi.org/10.1186/s13046-021-01901-1] [PMID: 33823894]
[22]
Moribe F, Nishikori M, Takashima T, et al. Epigenetic suppression of SLFN11 in germinal center B-cells during B-cell development. PLoS One 2021; 16(1): e0237554.
[http://dx.doi.org/10.1371/journal.pone.0237554] [PMID: 33513156]
[23]
Scholze H, Stephenson RE, Reynolds R, et al. Combined EZH2 and Bcl-2 inhibitors as precision therapy for genetically defined DLBCL subtypes. Blood Adv 2020; 4(20): 5226-31.
[http://dx.doi.org/10.1182/bloodadvances.2020002580] [PMID: 33104794]
[24]
Sarkozy C, Morschhauser F, Dubois S, et al. A LYSA phase ib study of tazemetostat (epz-6438) plus R-CHOP in patients with newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) with poor prognosis features. Clin Cancer Res 2020; 26(13): 3145-53.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-3741] [PMID: 32122924]
[25]
Tan X, Zhang Z, Liu P, Yao H, Shen L, Tong JS. Inhibition of EZH2 enhances the therapeutic effect of 5-FU via PUMA upregulation in colorectal cancer. Cell Death Dis 2020; 11(12): 1061.
[http://dx.doi.org/10.1038/s41419-020-03266-3] [PMID: 33311453]
[26]
Lo Sardo F, Pulito C, Sacconi A, et al. YAP/TAZ and EZH2 synergize to impair tumor suppressor activity of TGFBR2 in non-small cell lung cancer. Cancer Lett 2021; 500: 51-63.
[http://dx.doi.org/10.1016/j.canlet.2020.11.037] [PMID: 33296708]
[27]
Fu H, Cheng L, Sa R, Jin Y, Chen L. Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAFV600E by synergistically decreasing global trimethylation of H3K27. J Cell Mol Med 2020; 24(6): 3336-45.
[http://dx.doi.org/10.1111/jcmm.15007] [PMID: 31970877]
[28]
Stazi G, Taglieri L, Nicolai A, et al. Dissecting the role of novel EZH2 inhibitors in primary glioblastoma cell cultures: Effects on proliferation, epithelial-mesenchymal transition, migration, and on the pro-inflammatory phenotype. Clin Epigenetics 2019; 11(1): 1-17.
[http://dx.doi.org/10.1186/s13148-019-0763-5]
[29]
Tansir G, Rastogi S, Shamim SA, Barwad A. Early clinical and metabolic response to tazemetostat in advanced relapsed INI1 negative epithelioid sarcoma. Future Sci OA 2021; 7(4): FSO675.
[http://dx.doi.org/10.2144/fsoa-2020-0173] [PMID: 33815821]
[30]
Munakata W, Shirasugi Y, Tobinai K, et al. Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma. Cancer Sci 2021; 112(3): 1123-31.
[http://dx.doi.org/10.1111/cas.14822] [PMID: 33492746]
[31]
Gounder M, Schöffski P, Jones RL, et al. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: An international, open-label, phase 2 basket study. Lancet Oncol 2020; 21(11): 1423-32.
[http://dx.doi.org/10.1016/S1470-2045(20)30451-4] [PMID: 33035459]
[32]
Gounder MM, Zhu G, Roshal L, et al. Immunologic correlates of the abscopal effect in a SMARCB1/INI1-negative poorly differentiated chordoma after EZH2 inhibition and radiotherapy. Clin Cancer Res 2019; 25(7): 2064-71.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-3133] [PMID: 30642912]
[33]
Pecora A, Halpern S, Weber M, et al. Rapid and complete response to combination Anti-CTLA-4 and Anti-PD-1 checkpoint inhibitor therapy in a patient with stage IV refractory end-stage epithelioid sarcoma: A case report. J Immunother 2020; 43(9): 286-90.
[http://dx.doi.org/10.1097/CJI.0000000000000332] [PMID: 32815894]
[34]
Mola S, Pinton G, Erreni M, et al. Inhibition of the histone methyltransferase EZH2 enhances protumor monocyte recruitment in human mesothelioma spheroids. Int J Mol Sci 2021; 22(9): 4391.
[http://dx.doi.org/10.3390/ijms22094391] [PMID: 33922336]
[35]
Makita S, Hosoba R, Tobinai K. Safety considerations with targeted therapy drugs for B-cell non-Hodgkin lymphoma. Expert Opin Drug Saf 2020; 19(9): 1105-20.
[http://dx.doi.org/10.1080/14740338.2020.1802424] [PMID: 32715803]
[36]
Prokopuk L, Hogg K, Western PS. Pharmacological inhibition of EZH2 disrupts the female germline epigenome. Clin Epigenetics 2018; 10(1): 33.
[http://dx.doi.org/10.1186/s13148-018-0465-4] [PMID: 29515677]
[37]
Lee S, Woo DC, Kang J, et al. The role of the histone methyltransferase EZH2 in liver inflammation and fibrosis in STAM NASH mice. Biology (Basel) 2020; 9(5): 93.
[http://dx.doi.org/10.3390/biology9050093] [PMID: 32370249]

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