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Overview of Ferroptosis and Synthetic Lethality Strategies
Ferroptosis, a term first proposed in 2012, is iron-dependent, non-apoptotic regulatory cell death induced by erastin. Ferroptosis was originally discovered during synthetic lethal screening for drugs sensitive to RAS mutant cells, and is closely related to synthetic lethality. Ferroptosis sensitize...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430824/ https://www.ncbi.nlm.nih.gov/pubmed/34502181 http://dx.doi.org/10.3390/ijms22179271 |
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author | Kinowaki, Yuko Taguchi, Towako Onishi, Iichiroh Kirimura, Susumu Kitagawa, Masanobu Yamamoto, Kouhei |
author_facet | Kinowaki, Yuko Taguchi, Towako Onishi, Iichiroh Kirimura, Susumu Kitagawa, Masanobu Yamamoto, Kouhei |
author_sort | Kinowaki, Yuko |
collection | PubMed |
description | Ferroptosis, a term first proposed in 2012, is iron-dependent, non-apoptotic regulatory cell death induced by erastin. Ferroptosis was originally discovered during synthetic lethal screening for drugs sensitive to RAS mutant cells, and is closely related to synthetic lethality. Ferroptosis sensitizes cancer stem cells and tumors that undergo epithelial−mesenchymal transition and are resistant to anticancer drugs or targeted therapy. Therefore, ferroptosis-inducing molecules are attractive new research targets. In contrast, synthetic lethal strategies approach mechanisms and genetic abnormalities that cannot be directly targeted by conventional therapeutic strategies, such as RAS mutations, hypoxia, and abnormalities in the metabolic environment. They also target the environment and conditions specific to malignant cells, have a low toxicity to normal cells, and can be used in combination with known drugs to produce new ones. However, the concept of synthetic lethality has not been widely adopted with ferroptosis. In this review, we surveyed the literature on ferroptosis-related factors and synthetic lethality to examine the potential therapeutic targets in ferroptosis-related molecules, focusing on factors related to synthetic lethality, discovery methods, clinical application stages, and issues in drug discovery. |
format | Online Article Text |
id | pubmed-8430824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84308242021-09-11 Overview of Ferroptosis and Synthetic Lethality Strategies Kinowaki, Yuko Taguchi, Towako Onishi, Iichiroh Kirimura, Susumu Kitagawa, Masanobu Yamamoto, Kouhei Int J Mol Sci Review Ferroptosis, a term first proposed in 2012, is iron-dependent, non-apoptotic regulatory cell death induced by erastin. Ferroptosis was originally discovered during synthetic lethal screening for drugs sensitive to RAS mutant cells, and is closely related to synthetic lethality. Ferroptosis sensitizes cancer stem cells and tumors that undergo epithelial−mesenchymal transition and are resistant to anticancer drugs or targeted therapy. Therefore, ferroptosis-inducing molecules are attractive new research targets. In contrast, synthetic lethal strategies approach mechanisms and genetic abnormalities that cannot be directly targeted by conventional therapeutic strategies, such as RAS mutations, hypoxia, and abnormalities in the metabolic environment. They also target the environment and conditions specific to malignant cells, have a low toxicity to normal cells, and can be used in combination with known drugs to produce new ones. However, the concept of synthetic lethality has not been widely adopted with ferroptosis. In this review, we surveyed the literature on ferroptosis-related factors and synthetic lethality to examine the potential therapeutic targets in ferroptosis-related molecules, focusing on factors related to synthetic lethality, discovery methods, clinical application stages, and issues in drug discovery. MDPI 2021-08-27 /pmc/articles/PMC8430824/ /pubmed/34502181 http://dx.doi.org/10.3390/ijms22179271 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Kinowaki, Yuko Taguchi, Towako Onishi, Iichiroh Kirimura, Susumu Kitagawa, Masanobu Yamamoto, Kouhei Overview of Ferroptosis and Synthetic Lethality Strategies |
title | Overview of Ferroptosis and Synthetic Lethality Strategies |
title_full | Overview of Ferroptosis and Synthetic Lethality Strategies |
title_fullStr | Overview of Ferroptosis and Synthetic Lethality Strategies |
title_full_unstemmed | Overview of Ferroptosis and Synthetic Lethality Strategies |
title_short | Overview of Ferroptosis and Synthetic Lethality Strategies |
title_sort | overview of ferroptosis and synthetic lethality strategies |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430824/ https://www.ncbi.nlm.nih.gov/pubmed/34502181 http://dx.doi.org/10.3390/ijms22179271 |
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