The experimental development of bioreductive drugs and their role in cancer therapy.
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.
Workman
P
P
Cancer Research Campaign Beatson Laboratories, CRC Department of Medical Oncology, University of Glasgow, Bearsden, United Kingdom.
Stratford
I J
IJ
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D001388:Aziridines / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004249:DNA Damage; D006801:Humans; D045563:Indolequinones; D007211:Indoles / Q000627:therapeutic use; D008920:Misonidazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use* / Q000633:toxicity; D000077704:Tirapazamine; D014227:Triazines / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001388:Aziridines; D045563:Indolequinones; D007211:Indoles; D011838:Radiation-Sensitizing Agents; D014227:Triazines; D000077704:Tirapazamine; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole; C060817:apaziquone