Last but not least: BFL-1 as an emerging target for anti-cancer therapies.
Biochem Soc Trans
; 50(4): 1119-1128, 2022 08 31.
Article
em En
| MEDLINE
| ID: mdl-35900226
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-bcl-2
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article