The Combination of the PARP Inhibitor Rucaparib and 5FU Is an Effective Strategy for Treating Acute Leukemias

Maria V ittoria Verga Falzacappa, Chiara Ronchini, Mario Faretta, Ilaria Iacobucci, Andrea G helli Luserna Di Rorà, Giovanni Martinelli, Lüder Hinrich Meyer, Klaus Michael Debatin, Stefania Orecchioni, Francesco Bertolini, Pier G iuseppe Pelicci

Research output: Contribution to journalArticlepeer-review


The existing treatments to cure acute leukemias seem to be nonspecific 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 their 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.

Original languageEnglish
Pages (from-to)889-898
Number of pages10
JournalMolecular Cancer Therapeutics
Issue number4
Publication statusPublished - Apr 1 2015

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'The Combination of the PARP Inhibitor Rucaparib and 5FU Is an Effective Strategy for Treating Acute Leukemias'. Together they form a unique fingerprint.

Cite this