THE EXPERIMENTAL DEVELOPMENT OF BIOREDUCTIVE DRUGS AND THEIR ROLE IN CANCER-THERAPY

被引:152
作者
WORKMAN, P
STRATFORD, IJ
机构
[1] MRC,RADIOBIOL UNIT,DIDCOT OX11 0RD,OXON,ENGLAND
[2] UNIV GLASGOW,CANC RES CAMPAIGN,BEATSON LABS,CRC DEPT MED ONCOL,GLASGOW G6 1BD,SCOTLAND
基金
英国医学研究理事会;
关键词
BIOREDUCTION; HYPOXIA; REDUCTASES; THERAPY;
D O I
10.1007/BF00689802
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bioreductive drugs undergo metabolic reduction to generate cytotoxic metabolites. This process is facilitated by bioreductive enzymes and the lower oxygen conditions present in solid tumours compared to normal tissues. Because of this specificity, bioreductive drugs have enormous potential to contribute to modern cancer therapy. Examples undergoing clinical trials include N-oxides such as tirapazamine, aziridinylnitroimidazoles RSU 1069/RBU 6145 and quinones such as indoloquinone EO9. Other novel structures are also under study. Here we review the experimental development of bioreductive drugs and their role in cancer therapy.
引用
收藏
页码:73 / 82
页数:10
相关论文
共 85 条
[1]   BIOREDUCTIVE DRUGS AS POSTIRRADIATION SENSITIZERS - COMPARISON OF DUAL FUNCTION AGENTS WITH SR-4233 AND THE MITOMYCIN-C ANALOG-EO9 [J].
ADAMS, GE ;
STRATFORD, IJ ;
EDWARDS, HS ;
BREMNER, JCM ;
COLE, S .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1992, 22 (04) :717-720
[2]  
ADAMS GE, 1980, J NATL CANCER I, V64, P555
[3]   RADIATION SENSITIZATION AND CHEMOPOTENTIATION - RSU-1069, A COMPOUND MORE EFFICIENT THAN MISONIDAZOLE INVITRO AND INVIVO [J].
ADAMS, GE ;
AHMED, I ;
SHELDON, PW ;
STRATFORD, IJ .
BRITISH JOURNAL OF CANCER, 1984, 49 (05) :571-577
[4]   MAMMALIAN-CELL TOXICITY OF NITRO-COMPOUNDS - DEPENDENCE UPON REDUCTION POTENTIAL [J].
ADAMS, GE ;
CLARKE, ED ;
JACOBS, RS ;
STRATFORD, IJ ;
WALLACE, RG ;
WARDMAN, P ;
WATTS, ME .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1976, 72 (03) :824-829
[5]  
ADAMS GE, 1992, RAD RES 20TH CENTURY, V2, P802
[6]   STRUCTURE-ACTIVITY-RELATIONSHIPS FOR DT-DIAPHORASE REDUCTION OF HYPOXIC CELL DIRECTED AGENTS - INDOLOQUINONES AND DIAZIRIDINYL BENZOQUINONES [J].
BAILEY, SM ;
SUGGETT, N ;
WALTON, MI ;
WORKMAN, P .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1992, 22 (04) :649-653
[7]   INCREASED SENSITIVITY OF QUINONE RESISTANT CELLS TO MITOMYCIN-C [J].
BEGLEITER, A ;
ROBOTHAM, E ;
LACEY, G ;
LEITH, MK .
CANCER LETTERS, 1989, 45 (03) :173-176
[8]   SR-4233 CYTOTOXICITY AND METABOLISM IN DNA REPAIR-COMPETENT AND REPAIR-DEFICIENT CELL-CULTURES [J].
BIEDERMANN, KA ;
WANG, J ;
GRAHAM, RP ;
BROWN, JM .
BRITISH JOURNAL OF CANCER, 1991, 63 (03) :358-362
[9]  
BREMNER JCM, 1990, BRIT J CANCER, V61, P177
[10]  
BROWN JM, 1991, RADIOTHER ONCOL, V20, P151