期刊
BIOCHEMICAL SOCIETY TRANSACTIONS
卷 50, 期 4, 页码 1119-1128出版社
PORTLAND PRESS LTD
DOI: 10.1042/BST20220153
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资金
- Australian National Health and Medical Research Council (NHMRC) [1186575, 1145728, 1143105, 1159658, 1156095]
- Leukaemia and Lymphoma Society of America (LLS SCOR) [7015-18]
- Cancer Council of Victoria [AppID-000012]
- Australian Phenomics Network
- Victorian Cancer Agency (Early-Career Fellowship) [21006]
- CASS Foundation
BFL-1, an understudied pro-survival BCL-2 protein, is expressed in many cancers. However, it is unclear whether high transcript expression always correlates with cell survival function. Recent research suggests that BFL-1 may be a resistance factor in blood cancers, highlighting the importance of understanding its role and resistance mechanisms in human cancers. Currently, there are no effective BFL-1 inhibitors available.
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 BH3mimetics 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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