Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer
Details
Publication Year 2015-08-10,Volume 35,Issue #15,Page 1877-87
Journal Title
Oncogene
Publication Type
Journal Article
Abstract
The last three decades have seen significant progress in our understanding of the role of the pro-survival protein BCL-2 and its family members in apoptosis and cancer. BCL-2 and other pro-survival family members including Mcl-1 and BCL-XL have been shown to have a key role in keeping pro-apoptotic 'effector' proteins BAK and BAX in check. They also neutralize a group of 'sensor' proteins (such as BIM), which are triggered by cytotoxic stimuli such as chemotherapy. BCL-2 proteins therefore have a central role as guardians against apoptosis, helping cancer cells to evade cell death. More recently, an increasing number of BH3 mimetics, which bind and neutralize BCL-2 and/or its pro-survival relatives, have been developed. The utility of targeting BCL-2 in hematological malignancies has become evident in early-phase studies, with remarkable clinical responses seen in heavily pretreated patients. As BCL-2 is overexpressed in ~75% of breast cancer, there has been growing interest in determining whether this new class of drug could show similar promise in breast cancer. This review summarizes our current understanding of the role of BCL-2 and its family members in mammary gland development and breast cancer, recent progress in the development of new BH3 mimetics as well as their potential for targeting estrogen receptor-positive breast cancer.Oncogene advance online publication, 10 August 2015; doi:10.1038/onc.2015.287.
Publisher
NPG
Research Division(s)
Stem Cells And Cancer
PubMed ID
26257067
NHMRC Grants
NHMRC/1016701NHMRC/1040978NHMRC/1078730
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-08-21 12:29:36
Last Modified: 2016-12-14 10:20:09
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