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Pharmaceuticals

Directing Cancer Drug Cisplatin To Mitochondria Kills Resistant Tumor Cells

Tests in cell culture suggest another way that platinum-based chemotherapies can work

by Carmen Drahl
November 18, 2013 | APPEARED IN VOLUME 91, ISSUE 46

Nearly half of all cancer patients receive a platinum-based drug such as cisplatin as part of their chemotherapy. Although lifesaving for many, the drugs have serious side effects, including kidney damage. Some tumors also become resistant to the treatments. Cisplatin kills cancer cells by cross-linking DNA in their nuclei. But a team led by Stephen J. Lippard of MIT and Shana O. Kelley of the University of Toronto wondered whether targeting cisplatin to another organelle, the mitochondrion, might mitigate the drug’s shortcomings. Mitochondria seem to contribute to certain cancers’ resistance to cisplatin. What’s more, mitochondria are players in the programmed cell death process called apoptosis. To test the idea, Lippard and Kelley’s team combined a cisplatin motif with a cationic, lipophilic peptide that targets mitochondria (Chem. Biol. 2013, DOI: 10.1016/j.chembiol.2013.08.010). Sure enough, the resulting conjugate, mtPt, killed cisplatin-resistant ovarian cancer cells. The conjugate induced apoptosis in cancer cell cultures without damaging nuclear DNA, which suggests that cross-linking mitochondrial DNA alone is a sufficient strategy. Lippard and Kelley each have patents covering aspects of mtPt. Now they’re organizing studies to evaluate the compound in animals.

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