Piercing the armor of hepatobiliary cancer: Bcl-2 homology domain 3 (BH3) mimetics and cell death
✍ Scribed by Justin L. Mott; Gregory J. Gores
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 284 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
ne of the cardinal features that cells acquire at malignant transformation is the ability to resist apoptosis in an overtly toxic environment. Cancerous cells survive and proliferate despite internal stresses such as gross genetic alterations and external insults including immune attack, relative hypoxia, and competition for nutrients. The evasion of cell death in this environment is as remarkable as it is necessary, and is responsible for the resistance of cancers to existing therapies. However, the mechanisms of resistance are currently being revealed. One protein family, the B cell lymphoma 2 (Bcl-2) family, has emerged as a dominant regulator of apoptosis in cancer cells. In hepatocellular carcinoma, members of this family are dysregulated, not by direct mutations, but as the downstream consequence of perturbed signaling cascades. 1 For example, Bcl-x L protein expression is augmented by enhanced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. 2,3 Likewise, although information is more limited, the same trend of signaling-induced alterations in Bcl-2 family member expression appears to be true for cholangiocarcinoma. [4][5][6] In this regard, hepatobiliary cancers are like most other malignancies and are addicted to Bcl-2 family proteins. This article discusses specific recent advances in overcoming resistance to apoptosis by antiapoptotic Bcl-2 family proteins, especially as it relates to targeting these proteins for treatment of hepatobiliary malignancies.