BCL-2 protein family: attractive targets for cancer therapy

被引:248
作者
Kaloni, Deeksha [1 ,2 ]
Diepstraten, Sarah T. [1 ]
Strasser, Andreas [1 ,2 ]
Kelly, Gemma L. [1 ,2 ]
机构
[1] Walter & Eliza Hall Inst Med Res, Blood Cells & Blood Canc Div, Melbourne, Vic, Australia
[2] Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia
基金
英国医学研究理事会;
关键词
Apoptosis; BCL-2 protein family; Pro-survival BCL-2 proteins; Pro-apoptotic BCL-2 family members; BH3-only proteins; BH3-mimetic drugs; CHRONIC LYMPHOCYTIC-LEUKEMIA; VENETOCLAX PLUS RITUXIMAB; ANTI-APOPTOTIC MCL-1; CELL-DEATH; BH3-ONLY PROTEIN; KAPPA-B; UP-REGULATION; DOWN-REGULATION; IN-VITRO; X-L;
D O I
10.1007/s10495-022-01780-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Acquired resistance to cell death is a hallmark of cancer. The BCL-2 protein family members play important roles in controlling apoptotic cell death. Abnormal over-expression of pro-survival BCL-2 family members or abnormal reduction of pro-apoptotic BCL-2 family proteins, both resulting in the inhibition of apoptosis, are frequently detected in diverse malignancies. The critical role of the pro-survival and pro-apoptotic BCL-2 family proteins in the regulation of apoptosis makes them attractive targets for the development of agents for the treatment of cancer. This review describes the roles of the various pro-survival and pro-apoptotic members of the BCL-2 protein family in normal development and organismal function and how defects in the control of apoptosis promote the development and therapy resistance of cancer. Finally, we discuss the development of inhibitors of pro-survival BCL-2 proteins, termed BH3-mimetic drugs, as novel agents for cancer therapy.
引用
收藏
页码:20 / 38
页数:19
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