Resistance to venetoclax and hypomethylating agents in acute myeloid leukemia  

作　　者：Antoine N.Saliba August J.John Scott H.Kaufmann 

机构地区：[1]Division of Hematology,Department of Medicine,Mayo Clinic,Rochester,MN 55905,USA [2]Department of Molecular Pharmacology and Experimental Therapeutics,Mayo Clinic,Rochester,MN 55905,USA [3]Division of Oncology Research,Department of Oncology,Mayo Clinic,Rochester,MN 55905,USA

出　　处：《Cancer Drug Resistance》2021年第1期125-142,共18页癌症耐药（英文）

摘　　要：Despite the success of the combination of venetoclax with the hypomethylating agents(HMA)decitabine or azacitidine in inducing remission in older,previously untreated patients with acute myeloid leukemia(AML),resistance-primary or secondary-still constitutes a significant roadblock in the quest to prolong the duration of response.Here we review the proposed and proven mechanisms of resistance to venetoclax monotherapy,HMA monotherapy,and the doublet of venetoclax and HMA for the treatment of AML.We approach the mechanisms of resistance to HMAs and venetoclax in the light of the agents’mechanisms of action.We briefly describe potential therapeutic strategies to circumvent resistance to this promising combination,including alternative scheduling or the addition of other agents to the HMA and venetoclax backbone.Understanding the mechanisms of action and evolving resistance in AML remains a priority in order to maximize the benefit from novel drugs and combinations,identify new therapeutic targets,define potential prognostic markers,and avoid treatment failure.

关 键 词：Venetoclax hypomethylating agents RESISTANCE acute myeloid leukemia AZACITIDINE DECITABINE 

分 类 号：R73[医药卫生—肿瘤]