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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

Author

Listed:
  • Donna L Nile
  • Colin Rae
  • 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)

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.

Suggested Citation

  • Donna L Nile & Colin Rae & Robert J Mairs & Colin Nixon & Mark N Gaze, 2018. "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," Cancer Therapy & Oncology International Journal, Juniper Publishers Inc., vol. 10(3), pages 44-48, May.
    • Handle: RePEc:adp:jctoij:v:10:y:2018:i:3:p:44-48
    DOI: 10.19080/CTOIJ.2018.10.555788
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