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

For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with (177)Lu-[DOTA0-Tyr3]-octreotate ((177)Lu-octreotate) is one of the most promising targeted therapeutic options but it rarely achieves cure. Therefore, differ...

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Autores principales: Purohit, Nupur K., Shah, Rashmi G., Adant, Samuel, Hoepfner, Michael, Shah, Girish M., Beauregard, Jean-Mathieu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973847/
https://www.ncbi.nlm.nih.gov/pubmed/29872498
http://dx.doi.org/10.18632/oncotarget.25266
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author Purohit, Nupur K.
Shah, Rashmi G.
Adant, Samuel
Hoepfner, Michael
Shah, Girish M.
Beauregard, Jean-Mathieu
author_facet Purohit, Nupur K.
Shah, Rashmi G.
Adant, Samuel
Hoepfner, Michael
Shah, Girish M.
Beauregard, Jean-Mathieu
author_sort Purohit, Nupur K.
collection PubMed
description For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with (177)Lu-[DOTA0-Tyr3]-octreotate ((177)Lu-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 (177)Lu-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 (177)Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing (177)Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of (177)Lu-octreotate PRRT of NETs.
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spelling pubmed-59738472018-06-05 Potentiation of (177)Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor Purohit, Nupur K. Shah, Rashmi G. Adant, Samuel Hoepfner, Michael Shah, Girish M. Beauregard, Jean-Mathieu Oncotarget Research Paper For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with (177)Lu-[DOTA0-Tyr3]-octreotate ((177)Lu-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 (177)Lu-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 (177)Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing (177)Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of (177)Lu-octreotate PRRT of NETs. Impact Journals LLC 2018-05-15 /pmc/articles/PMC5973847/ /pubmed/29872498 http://dx.doi.org/10.18632/oncotarget.25266 Text en Copyright: © 2018 Purohit et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Purohit, Nupur K.
Shah, Rashmi G.
Adant, Samuel
Hoepfner, Michael
Shah, Girish M.
Beauregard, Jean-Mathieu
Potentiation of (177)Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor
title Potentiation of (177)Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor
title_full Potentiation of (177)Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor
title_fullStr Potentiation of (177)Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor
title_full_unstemmed Potentiation of (177)Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor
title_short Potentiation of (177)Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor
title_sort potentiation of (177)lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by parp inhibitor
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973847/
https://www.ncbi.nlm.nih.gov/pubmed/29872498
http://dx.doi.org/10.18632/oncotarget.25266
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