Scientists and clinicians test their metal-back to the future with platinum compounds.
After more than two decades of extensive use, drugs based on platinum continue to have a major role in cancer treatment. Although systematic approaches to the development of new analogues have produced agents with less toxicity and novel mechanisms of action, to date such approaches have not achieved more cures than can be achieved with the parent compound, cisplatin. Greater gains might be expected from accumulating knowledge about what makes cancer cells sensitive or resistant to platinum-based chemotherapy. Recent information on drug-efflux pathways, including expression of multidrug-resistance protein 2, and on how tumour cells behave when their DNA is distorted by a platinum adduct, suggests new avenues for translational research. The prospects include modulation of cellular handling of platinum compounds and individualised therapy based on expression of molecules that determine platinum sensitivity.
Guminski
Alexander D
AD
Department of Medical Oncology and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead Hospital, NSW 2145, Australia. alexg@westgate.wh.usyd.edu.au
Harnett
Paul R
PR
deFazio
Anna
A
D002470:Cell Survival / Q000187:drug effects; D002986:Clinical Trials as Topic; D018736:DNA Adducts / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009944:Organoplatinum Compounds / Q000494:pharmacology*
D018736:DNA Adducts; D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds