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

doi:10.3390/cancers15030915

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 journal › Article › Academic › peer-review

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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 language	English
Article number	915
Journal	Cancers
Volume	15
Issue number	3
DOIs	https://doi.org/10.3390/cancers15030915
Publication status	Published - 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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cancers-15-00915Final published version, 1.88 MBLicence: CC BY

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title = "In Vivo Efficacy Testing of Peptide Receptor Radionuclide Therapy Radiosensitization Using Olaparib",

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.",

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

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AU - Feijtel, Danny

AU - Reuvers, Thom G A

AU - van Tuyll-van Serooskerken, Christine

AU - de Ridder, Corrina M A

AU - Stuurman, Debra C

AU - de Blois, Erik

AU - Verkaik, Nicole S

AU - de Bruijn, Peter

AU - Koolen, Stijn L W

AU - de Jong, Marion

AU - Nonnekens, Julie

N1 - 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.

PY - 2023/2/1

Y1 - 2023/2/1

N2 - 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.

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

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