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Ferroptosis: the vulnerability within a cancer monster
Treatment-resistant cancer, such as neuroendocrine prostate cancer (NEPC), is a lethal disease with limited therapeutic options. RB1 is a tumor suppressor gene that is lost in a majority of NEPC tumors. In this issue of the JCI, Wang and colleagues examined how RB1 loss may sensitize cancer cells to...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Clinical Investigation
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178832/ https://www.ncbi.nlm.nih.gov/pubmed/37183818 http://dx.doi.org/10.1172/JCI170027 |
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author | Xie, Wanqing Agarwal, Shivani Yu, Jindan |
author_facet | Xie, Wanqing Agarwal, Shivani Yu, Jindan |
author_sort | Xie, Wanqing |
collection | PubMed |
description | Treatment-resistant cancer, such as neuroendocrine prostate cancer (NEPC), is a lethal disease with limited therapeutic options. RB1 is a tumor suppressor gene that is lost in a majority of NEPC tumors. In this issue of the JCI, Wang and colleagues examined how RB1 loss may sensitize cancer cells to ferroptosis inducers through elevation of ACSL4, a key enzyme that promotes lipid peroxidation and triggers ferroptosis. We discuss a high potential of RB1-deficient cells to undergo ferroptosis due to the elevation of ACSL4. This is normally kept in check by abundant expression of GPX4, an antioxidant enzyme, in cancer cells. This balance, however, is tilted by GPX4 inhibitors, leading to massive ferroptosis. We highlight possible therapeutic strategies that exploit this inherent vulnerability for targeting RB1-deficient, treatment-resistant cancer. |
format | Online Article Text |
id | pubmed-10178832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-101788322023-05-15 Ferroptosis: the vulnerability within a cancer monster Xie, Wanqing Agarwal, Shivani Yu, Jindan J Clin Invest Commentary Treatment-resistant cancer, such as neuroendocrine prostate cancer (NEPC), is a lethal disease with limited therapeutic options. RB1 is a tumor suppressor gene that is lost in a majority of NEPC tumors. In this issue of the JCI, Wang and colleagues examined how RB1 loss may sensitize cancer cells to ferroptosis inducers through elevation of ACSL4, a key enzyme that promotes lipid peroxidation and triggers ferroptosis. We discuss a high potential of RB1-deficient cells to undergo ferroptosis due to the elevation of ACSL4. This is normally kept in check by abundant expression of GPX4, an antioxidant enzyme, in cancer cells. This balance, however, is tilted by GPX4 inhibitors, leading to massive ferroptosis. We highlight possible therapeutic strategies that exploit this inherent vulnerability for targeting RB1-deficient, treatment-resistant cancer. American Society for Clinical Investigation 2023-05-15 /pmc/articles/PMC10178832/ /pubmed/37183818 http://dx.doi.org/10.1172/JCI170027 Text en © 2023 Xie et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Commentary Xie, Wanqing Agarwal, Shivani Yu, Jindan Ferroptosis: the vulnerability within a cancer monster |
title | Ferroptosis: the vulnerability within a cancer monster |
title_full | Ferroptosis: the vulnerability within a cancer monster |
title_fullStr | Ferroptosis: the vulnerability within a cancer monster |
title_full_unstemmed | Ferroptosis: the vulnerability within a cancer monster |
title_short | Ferroptosis: the vulnerability within a cancer monster |
title_sort | ferroptosis: the vulnerability within a cancer monster |
topic | Commentary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178832/ https://www.ncbi.nlm.nih.gov/pubmed/37183818 http://dx.doi.org/10.1172/JCI170027 |
work_keys_str_mv | AT xiewanqing ferroptosisthevulnerabilitywithinacancermonster AT agarwalshivani ferroptosisthevulnerabilitywithinacancermonster AT yujindan ferroptosisthevulnerabilitywithinacancermonster |