Emerging Epigenetic Therapeutic Targets in Acute Myeloid Leukemia
Overview
Affiliations
Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy for which treatment options have been largely limited to cytotoxic chemotherapy for the past four decades. Next-generation sequencing and other approaches have identified a spectrum of genomic and epigenomic alterations that contribute to AML initiation and maintenance. The key role of epigenetic modifiers and the reversibility of epigenetic changes have paved the way for evaluation of a new set of drug targets, and facilitated the design of novel candidate treatment strategies. More recently, seven new targeted therapies have been FDA-approved demonstrating successful implementation of the past decades' research. In this review, we will summarize the most recent advances in targeted therapeutics designed for a focused group of key epigenetic regulators in AML, outline their mechanism of action and their current status in clinical development. Furthermore, we will discuss promising new approaches for epigenetic targeted treatment in AML which are currently being tested in pre-clinical trials.
Advances in epigenetic alterations of chronic lymphocytic leukemia: from pathogenesis to treatment.
Zhang X, Wang H, Zhang Y, Wang X Clin Exp Med. 2024; 24(1):54.
PMID: 38492089 PMC: 10944427. DOI: 10.1007/s10238-023-01268-x.
Small-Molecule Compounds Boost CAR-T Cell Therapy in Hematological Malignancies.
Cao X, Jin X, Zhang X, Utsav P, Zhang Y, Guo R Curr Treat Options Oncol. 2023; 24(3):184-211.
PMID: 36701037 PMC: 9992085. DOI: 10.1007/s11864-023-01049-4.
Targeting BRD9 by I-BRD9 efficiently inhibits growth of acute myeloid leukemia cells.
Zhou L, Yao Q, Li H, Chen J Transl Cancer Res. 2022; 10(7):3364-3372.
PMID: 35116642 PMC: 8797396. DOI: 10.21037/tcr-21-42.
TAF1 inhibitor Bay-299 induces cell death in acute myeloid leukemia.
Zhou L, Yao Q, Ma L, Li H, Chen J Transl Cancer Res. 2022; 10(12):5307-5318.
PMID: 35116379 PMC: 8798726. DOI: 10.21037/tcr-21-2295.
Ruan Y, Kim H, Ogana H, Wan Z, Hurwitz S, Nichols C Front Oncol. 2021; 11:766888.
PMID: 34926269 PMC: 8671162. DOI: 10.3389/fonc.2021.766888.