Last but not least: BFL-1 as an emerging target for anti-cancer therapies
- Author(s)
- Wang, G; Diepstraten, ST; Herold, MJ;
- Details
- Publication Year 2022-07-28,Volume 50,Issue #4,Page 1119-1128
- Journal Title
- Biochemical Society Transactions
- 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.
- Publisher
- Portland Press
- Keywords
- BCL-2 proteins; cancer; cell death; chemotherapy
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 35900226
- Publisher's Version
- https://doi.org/10.1042/bst20220153
- Open Access at Publisher's Site
https://doi.org/10.1042/BST20220153- NHMRC Grants
- NHMRC/1145728, NHMRC/1143105,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-08-08 09:15:59
Last Modified: 2022-09-07 09:23:29