The Suppression of DNA Repair Induced by PARP-1 Inhibitors Rucaparib and Olaparib in Combination with the Radiopharmaceutical 131I-MIBG in Noradrenaline Transporter-Expressing Xenograft Tumors

Donna L Nile, Colin Rae, Robert J Mairs, Colin Nixon and Mark N Gaze
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Robert J Mairs: Radiation Oncology, Institute of Cancer Sciences, University of Glasgow, United Kingdom
Colin Nixon: Beatson Institute for Cancer Research, University of Glasgow, United Kingdom
Mark N Gaze: University College London Hospitals, United Kingdom

Cancer Therapy & Oncology International Journal, 2018, vol. 10, issue 3, 44-48

Abstract: Radioiodinated meta-iodobenzylguanidine (131I-MIBG) is an effective treatment for tumors that express the noradrenaline transporter (NAT); including neuroblastoma, phaeochromocytoma, and gut neuroendocrine tumors. We have previously shown in vitro that the efficacy of 131I-MIBG was enhanced following its combination with PARP-1 inhibitors, rucaparib or olaparib. In order to assess in vivo the therapeutic benefit of combined radiotherapy and PARP-1 inhibition, we have first established a reliable protocol for the administration of olaparib and rucaparib, in NAT-expressing tumour xenografts. PARP-1 inhibition in combination with 131I-MIBG therapy was well tolerated with limited toxicity. Furthermore, administration of both PARP-1 inhibitors as single agents inhibited DNA repair in a time-dependent manner. These preliminary results highlight the therapeutic potential of PARP-1 inhibitors in vivo, and indicate the feasibility of combining rucaparib or olaparib with 131I-MIBG for the treatment of neuroendocrine tumors in preclinical models.

Keywords: juniper publishers:oncology journals; oncology research journals; oncology journal articles; oncology and cancer case reports; oncology journal of clinical and experimental cancer research; open access; open access journals; Oncology International Journal; juniper publishers reivew (search for similar items in EconPapers)
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:adp:jctoij:v:10:y:2018:i:3:p:44-48

DOI: 10.19080/CTOIJ.2018.10.555788

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