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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...

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Autores principales: Wang, Gaoyuan, Diepstraten, Sarah T., Herold, Marco J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2022
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.
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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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