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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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Detalles Bibliográficos
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
Descripción
Sumario: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.