In Vivo Efficacy Testing of Peptide Receptor Radionuclide Therapy Radiosensitization Using Olaparib

Danny Feijtel, Thom G A Reuvers, Christine van Tuyll-van Serooskerken, Corrina M A de Ridder, Debra C Stuurman, Erik de Blois, Nicole S Verkaik, Peter de Bruijn, Stijn L W Koolen, Marion de Jong, Julie Nonnekens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
32 Downloads (Pure)

Abstract

Peptide receptor radionuclide therapy (PRRT), a form of internal targeted radiation treatment using [177Lu]Lu [DOTA0-Tyr3]octreotate, is used to treat patients with metastasized neuroendocrine tumors (NETs). Even though PRRT is now the second line of treatment for patients with metastasized NETs, the majority of patients will not be cured by the treatment. PRRT functions by inducing DNA damage upon radioactive decay and inhibition of DNA damage repair proteins could therefore be used as a strategy to potentiate PRRT. Previous work has shown promising results on the combination of PRRT with the PARP inhibitor olaparib in cell lines and mice and we have been taken the next step for further in vivo validation using two different xenografted mouse models. We observed that this combination therapy resulted in increased therapeutic efficacy only in one model and not the other. Overall, our findings indicate a tumor-type dependent anti-tumor response to the combination of PRRT and olaparib. These data emphasize the unmet need for the molecular stratification of tumors to predetermine the potential clinical value of combining PARP inhibition with PRRT.

Original languageEnglish
Article number915
JournalCancers
Volume15
Issue number3
DOIs
Publication statusPublished - 1 Feb 2023

Bibliographical note

Funding Information:
This work was supported by a grant from the Daniel den Hoed Foundation and by Advanced Accelerator Applications SA, a Novartis company.

Publisher Copyright:
© 2023 by the authors.

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