Targeting ferroptosis for leukemia therapy: exploring novel strategies from its mechanisms and role in leukemia based on nanotechnology

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Abstract

The latest findings in iron metabolism and the newly uncovered process of ferroptosis have paved the way for new potential strategies in anti-leukemia treatments. In the current project, we reviewed and summarized the current role of nanomedicine in the treatment and diagnosis of leukemia through a comparison made between traditional approaches applied in the treatment and diagnosis of leukemia via the existing investigations about the ferroptosis molecular mechanisms involved in various anti-tumor treatments. The application of nanotechnology and other novel technologies may provide a new direction in ferroptosis-driven leukemia therapies. The article explores the potential of targeting ferroptosis, a new form of regulated cell death, as a new therapeutic strategy for leukemia. It discusses the mechanisms of ferroptosis and its role in leukemia and how nanotechnology can enhance the delivery and efficacy of ferroptosis-inducing agents. The article not only highlights the promise of ferroptosis-targeted therapies and nanotechnology in revolutionizing leukemia treatment, but also calls for further research to overcome challenges and fully realize the clinical potential of this innovative approach. Finally, it discusses the challenges and opportunities in clinical applications of ferroptosis.

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Most cited references 456

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Cancer statistics, 2019

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.

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Ferroptosis: an iron-dependent form of nonapoptotic cell death.

Scott J. Dixon, Kathryn Lemberg, Michael Lamprecht … (2012)

Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.

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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

Suzy Torti, Donna D. Zhang, K.A. Woerpel … (2019)

Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.

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Author and article information

Contributors

Mahnaz Amiri: mahnazamiri96@yahoo.com

Journal

Journal ID (nlm-ta): Eur J Med Res

Journal ID (iso-abbrev): Eur J Med Res

Title: European Journal of Medical Research

Publisher: BioMed Central (London )

ISSN (Print): 0949-2321

ISSN (Electronic): 2047-783X

Publication date (Electronic): 9 April 2024

Publication date PMC-release: 9 April 2024

Publication date Collection: 2024

Volume: 29

Electronic Location Identifier: 224

Affiliations

[1 ]Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran

[2 ]Stem Cells and Regenerative Medicine Innovation Center, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran

[3 ]Department of Chemistry, Faculty of Science, University of Jiroft, ( https://ror.org/00mz6ad23) Jiroft, Iran

[4 ]Department of Medical Biochemical Analysis, Cihan University-Erbil, ( https://ror.org/03hevjm30) Kurdistan Region, Iraq

[5 ]Institute of Nano Science and Nano Technology, University of Kashan, ( https://ror.org/015zmr509) P.O. Box 87317-51167, Kashan, Iran

[6 ]Student Research Committee, Faculty of Allied Medicine, Kerman University of Medical Sciences, ( https://ror.org/02kxbqc24) Kerman, Iran

[7 ]Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Science, ( https://ror.org/02kxbqc24) Kerman, Iran

Article

Publisher ID: 1822

DOI: 10.1186/s40001-024-01822-7

PMC ID: 11003188

PubMed ID: 38594732

SO-VID: 1d3defc1-d305-4784-a0ff-7070a8062814

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 5 October 2023

Date accepted : 30 March 2024

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004621, Kerman University of Medical Sciences;

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ScienceOpen disciplines: Medicine

Keywords: ferroptosis,hematological malignancies,nanomedicine,ferroptosis inducers,novel strategies

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ScienceOpen disciplines: Medicine

Keywords: ferroptosis, hematological malignancies, nanomedicine, ferroptosis inducers, novel strategies

Targeting ferroptosis for leukemia therapy: exploring novel strategies from its mechanisms and role in leukemia based on nanotechnology

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Most cited references 456

Cancer statistics, 2019

Ferroptosis: an iron-dependent form of nonapoptotic cell death.

Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

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