Title: Dexrazoxane may prevent doxorubicin-induced DNA damage via depleting both topoisomerase II isoforms
Authors: Deng S, Yan T, Jendrny C, Nemecek A, Vincetic M, Gödtel-Armbrust U, Wojnowski L.
Reference: BMC Cancer. 2014 Nov 18;14:842. doi: 10.1186/1471-2407-14-842.
Background: The bisdioxopiperazine dexrazoxane (DRZ) prevents anthracycline-induced heart failure, but its clinical use is limited by uncertain cardioprotective mechanism and by concerns of interference with cancer response to anthracyclines and of long-term safety.
Conclusions: Taken together, our data support a model of anthracycline-induced heart failure caused by TOP2B-mediated DSB and of its prevention by DRZ via TOP2B degradation rather than via iron chelation. The depletion of TOP2B and TOP2A suggests an explanation for the reported DRZ interference with cancer response to anthracyclines and for DRZ side-effects.