Mechanism of drug resistance and strategy for Venetoclax in acute myeloid leukemia
Acute myeloid leukemia(AML)is a hematologic malignancy characterized by a low remission and short survival.Fortunately,various targeted drugs in recent year may improve this challenging scenario.Among them,Venetoclax,approved by the FDA in 2018,has significantly enhanced the responses in AML patients.As a BH3 mimic,Venclexta induces tumor cell death by selectively binding to BCL-2 and inhibiting its anti-apoptotic function.However,with the wide use of Venetoclax in various AML scenarios,drug resistance has gradually become an issue.The specific mechanism of drug resistance in tumor cells includes:downregulation of BCL-2 and upregulation of other anti-apoptotic proteins,downregulation of pro-apoptotic proteins within the BCL-2 family,and other mechanisms independent of BCL-2 family proteins.This review systematically explained the molecular mechanism underlying Venetoclax resistance in AML and summarized strategies for addressing these problems.
Venetoclaxdrug resistanceBCL-2 protein familyoxidative phosphorylationpathway activationmitochondria
NETL
NSTL
万方数据
