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Last but not least: BFL-1 as an emerging target for anti-cancer therapies
BFL-1 is an understudied pro-survival BCL-2 protein. The expression of BFL-1 is reported in many cancers, but it is yet to be clarified whether high transcript expression also always correlates with a pro-survival function. However, recent applications of BH3-mimetics for the treatment of blood canc...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444066/ https://www.ncbi.nlm.nih.gov/pubmed/35900226 http://dx.doi.org/10.1042/BST20220153 |
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author | Wang, Gaoyuan Diepstraten, Sarah T. Herold, Marco J. |
author_facet | Wang, Gaoyuan Diepstraten, Sarah T. Herold, Marco J. |
author_sort | Wang, Gaoyuan |
collection | PubMed |
description | BFL-1 is an understudied pro-survival BCL-2 protein. The expression of BFL-1 is reported in many cancers, but it is yet to be clarified whether high transcript expression also always correlates with a pro-survival function. However, recent applications of BH3-mimetics for the treatment of blood cancers identified BFL-1 as a potential resistance factor in this type of cancer. Hence, understanding the role of BFL-1 in human cancers and how its up-regulation leads to therapy resistance has become an area of great clinical relevance. In addition, deletion of the murine homologue of BFL-1, called A1, in mice showed only minimal impacts on the well-being of these animals, suggesting drugs targeting BFL-1 would exhibit limited on-target toxicities. BFL-1 therefore represents a good clinical cancer target. Currently, no effective BFL-1 inhibitors exist, which is likely due to the underappreciation of BFL-1 as a potential target in the clinic and lack of understanding of the BFL-1 protein. In this review, the roles of BFL-1 in the development of different types of cancers and drug resistant mechanisms are discussed and some recent advances in the generation of BFL-1 inhibitors highlighted. |
format | Online Article Text |
id | pubmed-9444066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94440662022-09-07 Last but not least: BFL-1 as an emerging target for anti-cancer therapies Wang, Gaoyuan Diepstraten, Sarah T. Herold, Marco J. Biochem Soc Trans Review Articles BFL-1 is an understudied pro-survival BCL-2 protein. The expression of BFL-1 is reported in many cancers, but it is yet to be clarified whether high transcript expression also always correlates with a pro-survival function. However, recent applications of BH3-mimetics for the treatment of blood cancers identified BFL-1 as a potential resistance factor in this type of cancer. Hence, understanding the role of BFL-1 in human cancers and how its up-regulation leads to therapy resistance has become an area of great clinical relevance. In addition, deletion of the murine homologue of BFL-1, called A1, in mice showed only minimal impacts on the well-being of these animals, suggesting drugs targeting BFL-1 would exhibit limited on-target toxicities. BFL-1 therefore represents a good clinical cancer target. Currently, no effective BFL-1 inhibitors exist, which is likely due to the underappreciation of BFL-1 as a potential target in the clinic and lack of understanding of the BFL-1 protein. In this review, the roles of BFL-1 in the development of different types of cancers and drug resistant mechanisms are discussed and some recent advances in the generation of BFL-1 inhibitors highlighted. Portland Press Ltd. 2022-08-31 2022-07-28 /pmc/articles/PMC9444066/ /pubmed/35900226 http://dx.doi.org/10.1042/BST20220153 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Articles Wang, Gaoyuan Diepstraten, Sarah T. Herold, Marco J. Last but not least: BFL-1 as an emerging target for anti-cancer therapies |
title | Last but not least: BFL-1 as an emerging target for anti-cancer therapies |
title_full | Last but not least: BFL-1 as an emerging target for anti-cancer therapies |
title_fullStr | Last but not least: BFL-1 as an emerging target for anti-cancer therapies |
title_full_unstemmed | Last but not least: BFL-1 as an emerging target for anti-cancer therapies |
title_short | Last but not least: BFL-1 as an emerging target for anti-cancer therapies |
title_sort | last but not least: bfl-1 as an emerging target for anti-cancer therapies |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444066/ https://www.ncbi.nlm.nih.gov/pubmed/35900226 http://dx.doi.org/10.1042/BST20220153 |
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