Oncotarget

Research Papers:

Potentiation of 177Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor

Nupur K. Purohit, Rashmi G. Shah, Samuel Adant, Michael Hoepfner, Girish M. Shah and Jean-Mathieu Beauregard _

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Oncotarget. 2018; 9:24693-24706. https://doi.org/10.18632/oncotarget.25266

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Abstract

Nupur K. Purohit1,2,3, Rashmi G. Shah1,2,3, Samuel Adant1,2,3,4,5, Michael Hoepfner6, Girish M. Shah1,2,3,* and Jean-Mathieu Beauregard2,4,5,*

1Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, Canada

2Cancer Research Center, Université Laval, Quebec City, Canada

3Neurosciences and Oncology Branches of CHU de Québec, Université Laval Research Center, Quebec City, Canada

4Department of Radiology and Nuclear Medicine, Université Laval, Quebec City, Canada

5Oncology Branch of CHU de Québec, Université Laval Research Center, Quebec City, Canada

6Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

*Senior authorship

Correspondence to:

Jean-Mathieu Beauregard, email: jean-mathieu.beauregard@chudequebec.ca

Keywords: peptide receptor radionuclide therapy; 177Lu-octreotate; neuroendocrine tumors; PARP inhibitor; radiosensitization

Received: November 08, 2017     Accepted: April 06, 2018     Published: May 15, 2018

ABSTRACT

For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with 177Lu-[DOTA0-Tyr3]-octreotate (177Lu-octreotate) is one of the most promising targeted therapeutic options but it rarely achieves cure. Therefore, different approaches are being tested to increase the efficacy of 177Lu-octreotate PRRT in NET patients. Using the gastroenteropancreatic BON-1 and the bronchopulmonary NCI-H727 as NET cell models, here we report that pharmacological inhibitors of DNA repair-associated enzyme poly(ADP-ribose) polymerase-1 (PARPi) potentiate the cytotoxic effect of 177Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing 177Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of 177Lu-octreotate PRRT of NETs.


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