Scientists and clinicians test their metal–back to the future with platinum compounds - 01/09/11

Doi : 10.1016/S1470-2045(02)00733-7

Alexander D Guminski, Dr ^a,^⁎ : doctoral student, Paul R Harnett ^a : Clinical Director, Anna deFazio ^b : clinical senior lecturer

^a Department of Medical Oncology and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia

^b Department of Gynaecological Oncology, University of Sydney at the Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia

^* Correspondence: Dr Alexander D Guminski, University of Sydney, Westmead Institute of Cancer Research, PO Box 533, Wentworthville, NSW 2145, Australia. Tel: +61 2 9845 6954. Fax: +61 2 9845 6391

Summary

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 multidrugresistance 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.

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