The combination of the PARP inhibitor rucaparib and 5FU is an effective strategy for treating acute leukemias
Menée in vitro et in vivo, cette étude suggère l'intérêt du rucaparib, un inhibiteur de PARP, en combinaison avec du 5-fluorouracile pour le traitement d'une leucémie myléoïde aiguë ou d'une leucémie lymphoïde aiguë
The existing treatments to cure acute leukemias seem to be non-specific and suboptimal for most patients, drawing attention to the need of new therapeutic strategies. In the last decade the anticancer potential of poly ADP-ribose polymerase (PARP) inhibitors became apparent and now several PARP inhibitors are being developed to treat various malignancies. So far the usage of PARP inhibitors has been mainly focused on the treatment of solid tumors and not too much about its efficacy on leukemias is known. In this study we test, for the first time on leukemic cells, a combined therapy that associates the conventional chemotherapeutic agent fluorouracil (5FU), used as a source of DNA damage, and a PARP inhibitor, rucaparib. We demonstrate the efficacy and the specificity of this combined therapy in killing both acute myeloid leukemia and acute lymphoid leukemia cells in vitro and in vivo. We clearly show that the inhibition of DNA repair induced by rucaparib is synthetic lethal with the DNA damage caused by 5FU in leukemic cells. Therefore, we propose a new therapeutic strategy able to enhance the cytotoxic effect of DNA-damaging agents in leukemia cells via inhibiting the repair of damaged DNA.
http://mct.aacrjournals.org/content/early/2015/02/07/1535-7163.MCT-14-0276.abstract