Mihăilă Romeo G
Faculty of Medicine, "Lucian Blaga" University of Sibiu, Hematology Department, Sibiu 550169, Romania.
Recent Pat Anticancer Drug Discov. 2023;18(1):11-28. doi: 10.2174/1574892817666220429105338.
Substantial progress in the therapeutic arsenal used to treat acute myeloid leukemia became possible in the last decade, as a result of advances in gene editing and descriptive and functional genomics.
The aim of this study is to analyze the efficacy and safety of venetoclax in the treatment of acute myeloid leukemia.
A mini-review was achieved using the articles published in PubMed and Web of Science in the last year, prior to 05.05.2021, which were searched using the terms "acute myeloid leukemia" and "venetoclax" and the new patents published in this field.
BCL-2 inhibitors administered in monotherapy are active against acute myeloid leukemia cells, but their efficacy is partially limited because they do not target other antiapoptotic proteins and venetoclax induced overexpression of the other antiapoptotic molecules. Venetoclax-based combinations (including those with hypomethylating agents) were able to improve outcomes for older patients with acute myeloid leukemia, including both remission rates and overall survival. Other drugs used in combination with venetoclax include: FLT3 inhibitors, IDH2 inhibitors, chidamide, ibrutinib, lapatinib, mivebresib, triptolide, metabolic inhibitors, nucleoside analogs, and classical chemotherapeutics. Both the mechanisms of venetoclax resistance and the ways to overcome it, as well as the adverse effects of venetoclax are analyzed.
The management of unfit and older patients with acute myeloid leukemia should be personalized and be the result of evaluating patient- and disease-specific factors that are essential to their care. Combinations that include venetoclax are an increasingly well-documented option for many of them.
由于基因编辑以及描述性和功能性基因组学的进展，过去十年中用于治疗急性髓系白血病的治疗手段取得了重大进展。
本研究旨在分析维奈克拉治疗急性髓系白血病的疗效和安全性。
使用2021年5月5日前一年在PubMed和Web of Science上发表的文章进行了一项小型综述，这些文章通过搜索“急性髓系白血病”和“维奈克拉”以及该领域新发表的专利来获取。
单药使用的BCL-2抑制剂对急性髓系白血病细胞有活性，但其疗效部分受限，因为它们不靶向其他抗凋亡蛋白，且维奈克拉会诱导其他抗凋亡分子的过表达。基于维奈克拉的联合治疗方案（包括与去甲基化药物联合）能够改善老年急性髓系白血病患者的预后，包括缓解率和总生存期。与维奈克拉联合使用的其他药物包括：FLT3抑制剂、IDH2抑制剂、西达本胺、伊布替尼、拉帕替尼、米韦溴司他、雷公藤内酯醇、代谢抑制剂、核苷类似物和传统化疗药物。分析了维奈克拉耐药的机制、克服耐药的方法以及维奈克拉的不良反应。
对不适合化疗的老年急性髓系白血病患者的管理应个体化，是评估对其治疗至关重要的患者和疾病特异性因素的结果。对于许多此类患者而言，包含维奈克拉的联合治疗方案越来越有充分的文献依据。
