Platinum and other metal coordination compounds in cancer chemotherapy. A commentary on the sixth international symposium: San Diego, California, 23-26th January 1991.
The use of molecular biological methodologies has provided a greater understanding of the cytotoxic effects of cisplatin and the underlying mechanisms of tumour cell resistance. Resistance to cisplatin is often multifocal with plasma membrane, cytosolic and nuclear components. Cisplatin-DNA adducts appear to be recognised by specific damage recognition proteins. Proteins associated with the transport of platinum through plasma membranes and genes associated with cisplatin resistance appear to be close to being elucidated. Current Phase I and Phase II clinical trials with platinum-containing complexes largely focus on the 1,2 diaminocyclohexane (DACH) carrier ligand, the dicarboxylatocyclobutane leaving group and complexes which circumvent cisplatin resistance in murine leukaemia models. At present, the trials are at too early a stage to allow comment on their clinical utility and, consequently, the relevance of the murine leukaemia-based preclinical observations. On the horizon, orally active platinum (IV) ammine/amine dicarboxylate dichloride coordination complexes with preclinical toxicological profiles similar to carboplatin should enter clinical trial in the next year.
McKeage
M J
MJ
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, UK.
Higgins
J D
JD
Kelland
L R
LR
D002945:Cisplatin / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004247:DNA; D018736:DNA Adducts; D004351:Drug Resistance; D010984:Platinum / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D010984:Platinum; D004247:DNA; D002945:Cisplatin