Cisplatin is a chemotherapy drug given to more than half of all cancer patients. The drug kills cells very effectively by damaging nuclear DNA, but if tumors become resistant to cisplatin they often grow back.
A new study from MIT and the University of Toronto offers a possible way to overcome that resistance. The researchers found that when cisplatin was delivered to cellular structures called mitochondria. DNA in this organelle was damaged, leading to cancer cell death. Moreover, the mitochondrial-targeted drug could overcome cisplatin resistance.
“These results suggest that the mitochondria can be an important target for platinum-based drugs,” says Robert Radford, an MIT postdoc and an author of a paper describing the findings in and online edition of the journal Biology & Chemistry.
Mitochondria-targeting cisplatin might also be effective at lower doses than regular cisplatin, helping to avoid some of the severe side effects often seen with the drug, according to the researchers.
Senior authors of the new paper are Stephen Lippard, the Arthur Amos Noyes Professor of Chemistry at MIT, and Shana Kelley, a professor of biochemistry and pharmaceutical sciences at the University of Toronto. Lead authors are Simon Wisnovsky, who received his PhD from the University of Toronto, and MIT alumnus Justin Wilson.
“This is the first study to isolate the effects of a platinum drug in mitochondria, and we were very intrigued to observe that the DNA damage caused by this drug outside of the nucleus were highly toxic,” Kelley says.