Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells

被引:33
作者
Oxford, SME
Dallman, CL
Johnson, PWM
Ganesan, A
Packham, G
机构
[1] Southampton Gen Hosp, Canc Res UK, Oncol Unit, Sch Med,Canc Sci Div, Southampton SO16 6YD, Hants, England
[2] Univ Southampton, Dept Chem, Combinatorial Ctr Excellence, Southampton SO17 1BJ, Hants, England
关键词
Bcl-2; apoptosis; cancer; antisense; small molecule; chemotherapy;
D O I
10.2174/0929867043455486
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
Apoptosis (or programmed cell death) is a genetically controlled "cell suicide" pathway which plays an essential role in deleting excess, unwanted or damaged cells during development and tissue homeostasis. Dysregulation of apoptosis contributes to a wide variety of pathological conditions, including AIDS, cardiovascular disease, infectious disease, autoimmunity and neurodegenerative disorders. Resistance to apoptosis is also a common feature in human malignancies, contributing to both the development of cancer and resistance to conventional therapies Such as radiation and cytotoxic drugs, which function by activating apoptotic cell death pathways. Bcl-2 is one of the best characterized cell death control proteins; its overexpression confers resistance to a broad range of apoptosis inducers and the cell survival functions of Bcl-2 are activated by translocation in lymphomas and overexpression in many other cancer types. A wealth of experimental data supports the idea that Bcl-2 is an attractive and tractable target for newer molecularly directed anti-cancer strategies, designed to promote cancer cell death. Here we review current understanding of the mechanism of action and importance of Bcl-2 in cancer cells and progress in developing new agents to target this key survival molecule.
引用
收藏
页码:1031 / 1040
页数:10
相关论文
共 93 条
[1]   Apoptosomes: engines for caspase activation [J].
Adams, JM ;
Cory, S .
CURRENT OPINION IN CELL BIOLOGY, 2002, 14 (06) :715-720
[2]   TRANSGENIC MODELS FOR HEMATOPOIETIC MALIGNANCIES [J].
ADAMS, JM ;
CORY, S .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (01) :9-31
[3]   Targeting death and decoy receptors of the tumour-necrosis factor superfamily [J].
Ashkenazi, A .
NATURE REVIEWS CANCER, 2002, 2 (06) :420-430
[4]   Prospects for targeting the Bcl-2 family of proteins to develop novel cytotoxic drugs [J].
Baell, JB ;
Huang, DCS .
BIOCHEMICAL PHARMACOLOGY, 2002, 64 (5-6) :851-863
[5]   Unwinding the loop of Bcl-2 phosphorylation [J].
Blagosklonny, MV .
LEUKEMIA, 2001, 15 (06) :869-874
[6]   The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions [J].
Borner, C .
MOLECULAR IMMUNOLOGY, 2003, 39 (11) :615-647
[7]  
BOYD JM, 1995, ONCOGENE, V11, P1921
[8]   Liposomal delivery of antisense oligonucleotides for efficient downregulation of Bcl-2 and induction of apoptosis [J].
Buck, AC ;
Shen, CX ;
Schirrmeister, H ;
Schmid-Kotsas, A ;
Munzert, G ;
Guhlmann, A ;
Mehrke, G ;
Klug, N ;
Gross, HJ ;
Bachem, M ;
Reske, SN .
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS, 2002, 17 (03) :281-289
[9]   Biochemical pathways of caspase activation during apoptosis [J].
Budihardjo, I ;
Oliver, H ;
Lutter, M ;
Luo, X ;
Wang, XD .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1999, 15 :269-290
[10]   Novel anticancer drug discovery [J].
Buolamwini, JK .
CURRENT OPINION IN CHEMICAL BIOLOGY, 1999, 3 (04) :500-509