EZH2 inhibition by tazemetostat: Mechanisms of action, safety and efficacy in relapsed/refractory follicular lymphoma Review
| Authors: | Julia, E.; Salles, G. |
| Review Title: | EZH2 inhibition by tazemetostat: Mechanisms of action, safety and efficacy in relapsed/refractory follicular lymphoma |
| Abstract: | Epigenetic alterations are major drivers of follicular lymphomagenesis, and these alterations are frequently caused by mutations in or upregulation of EZH2, a histone methyltransferase responsible for PRC2-mediated gene repression. EZH2 hyperactivation increases proliferation of B cells and prevents them from exiting the germinal center, favoring lymphomagenesis. The first FDA-approved EZH2 inhibitor is tazemetostat, which is orally available and targets both mutant and wild-type forms of the protein to induce cell cycle arrest and apoptosis of lymphoma cells in preclinical models. Phase II trials have shown objective response rates of 69% for patients with lymphoma-carrying EZH2 mutations and 35% for those with wild-type EZH2 without major toxicity, leading to tazemetostat approval for this cancer by the US FDA in June 2020. © 2021 |
| Keywords: | gene mutation; constipation; drug tolerability; fatigue; neutropenia; cancer recurrence; squamous cell carcinoma; area under the curve; ascites; diarrhea; drug efficacy; drug safety; gastrointestinal hemorrhage; hypertension; hypophosphatemia; nonhuman; drug approval; anorexia; cell proliferation; melanoma; metastasis; anemia; leukopenia; nausea; thrombocytopenia; vomiting; herpes zoster; antineoplastic activity; b lymphocyte; asthenia; backache; coughing; dizziness; dyspnea; fever; hyperglycemia; hyperuricemia; lymphocytopenia; hypoxia; lung embolism; acute kidney failure; hyperkalemia; hypokalemia; depression; germinal center; myelodysplastic syndrome; drug mechanism; epigenetics; drug response; urinary tract infection; pleura effusion; pancytopenia; headache; drug bioavailability; drug metabolism; intestine obstruction; lung infection; muscle spasm; b cells; dry skin; alopecia; empyema; follicular lymphoma; drug excretion; chronic kidney failure; hypertriglyceridemia; bronchitis; cerebrovascular accident; upper respiratory tract infection; cholestasis; adult respiratory distress syndrome; neuralgia; ezh2 gene; transcription factor ezh2; clinical outcome; device infection; septic shock; respiratory distress; vein occlusion; histone methylation; hyperamylasemia; acute myeloid leukemia; acute pancreatitis; upper abdominal pain; cholestatic hepatitis; faintness; noncardiac chest pain; human; priority journal; article; constrictive pericarditis; tazemetostat; maximum concentration; enhancer of zest homolog 2; liver cell damage |
| Journal Title: | Future Oncology |
| Volume: | 17 |
| Issue: | 17 |
| ISSN: | 1479-6694 |
| Publisher: | Future Medicine |
| Date Published: | 2021-06-01 |
| Start Page: | 2127 |
| End Page: | 2140 |
| Language: | English |
| DOI: | 10.2217/fon-2020-1244 |
| PUBMED: | 33709777 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2021 -- Source: Scopus |
