Impeding Cisplatin’s Power

New findings on cellular interactions of the chemotherapeutic agent cisplatin suggest ways the drug might be redesigned to have better potency and fewer side effects. Cisplatin is an important chemotherapy for severe connective tissue, lung, ovarian, and lymphatic solid tumors. But it has serious adverse side effects, and its tendency to bind cytoplasmic proteins diverts it from its main job—binding and damaging genomic DNA in cancer cell nuclei, killing the cells. Now, researchers led by Pernilla Wittung-Stafshede and Magnus Wolf-Watz of Umeå University, in Sweden, report that cisplatin binds in solution to Atox1, a chaperone protein that helps provide copper to newly biosynthesized metalloproteins, and causes Atox1 to slowly unfold and degrade (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1012899108). They also show that cancer cells that express higher levels of Atox1 are more resistant to cisplatin. Spending its precious time messing around with Atox1 may keep some administered cisplatin from reaching DNA, suggesting that inhibiting the interaction might be a good way to make the drug safer and more effective.