Póti, Ádám
Berta, Kinga
Xiao, Yonghong
Pipek, Orsolya
Klus, Gregory T.
Ried, Thomas
Csabai, István
Wilcoxen, Keith
Mikule, Keith
Szallasi, Zoltan
Szüts, Dávid http://orcid.org/0000-0001-7985-0136
Article History
Received: 10 March 2018
Revised: 28 September 2018
Accepted: 28 September 2018
First Online: 14 November 2018
Competing interests
: This work was partially funded by Tesaro. Y.X., K.W. and K.M. hold Tesaro stock. The other authors declare no competing interests.
: The authorisation to use animals in the CERFE facilities was obtained by The Direction des Services Vétérinaires, Ministère de l’Agriculture et de la Pêche, France (agreement No. B-91-228-107).
: PARP inhibitors are in use for the treatment of ovarian and breast cancer, and are undergoing trials on further cancer types. Due to their relatively mild side effects, PARP inhibitors have the potential for use in long-term maintenance treatment. However, inhibition of DNA repair with this family of drugs could potentially increase genomic mutagenesis, and the treatment-induced mutations could contribute to the development of resistance in the tumour or cause secondary malignancies in somatic cells. In this study, we used a combination of in vitro and in vivo approaches to show that long-term treatment with the PARP inhibitor niraparib has at most a minor mutagenic effect. In contrast to strongly mutagenic treatment with cisplatin, PARP inhibitors, therefore, represent a safer alternative for patients with good prognosis, and our results should increase the confidence in using PARP inhibitors for long-term treatments.