Targeting regulated cell death pathways in acute myeloid leukemia.

Content Provider	Europe PMC
Author	Garciaz, Sylvain Miller, Thomas Collette, Yves Vey, Norbert
Abstract	The use of the BCL2 inhibitor venetoclax has transformed the management of patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. By triggering intrinsic apoptosis, the drug is an excellent illustration of how our greater understanding of molecular cell death pathways can be translated into the clinic. Nevertheless, most venetoclax-treated patients will relapse, suggesting the need to target additional regulated cell death pathways. To highlight advances in this strategy, we review the recognized regulated cell death pathways, including apoptosis, necroptosis, ferroptosis and autophagy. Next, we detail the therapeutic opportunities to trigger regulated cell death in AML. Finally, we describe the main drug discovery challenges for regulated cell death inducers and their translation into clinical trials. A better knowledge of the molecular pathways regulating cell death represents a promising strategy to develop new drugs to cure resistant or refractory AML patients, particularly those resistant to intrinsic apoptosis.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC10099605&blobtype=pdf
Journal	Cancer Drug Resistance [Cancer Drug Resist]
Volume Number	6
DOI	10.20517/cdr.2022.108
PubMed Central reference number	PMC10099605
Issue Number	1
PubMed reference number	37065864
e-ISSN	2578532X
Language	English
Publisher	OAE Publishing Inc.
Publisher Date	2023-03-15
Access Restriction	Open
Rights License	© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. © The Author(s) 2023.
Subject Keyword	Acute myeloid leukemia regulated cell death apoptosis ferroptosis necroptosis autophagy
Content Type	Text
Resource Type	Article
Subject	Pharmacology (medical) Cancer Research