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

• Published in: Cancers Vol. 15; no. 3; p. 915
• Main Authors: Feijtel, Danny, Reuvers, Thom G A, van Tuyll-van Serooskerken, Christine, de Ridder, Corrina M A, Stuurman, Debra C, de Blois, Erik, Verkaik, Nicole S, de Bruijn, Peter, Koolen, Stijn L W, de Jong, Marion, Nonnekens, Julie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Animal models; Animals; Antigens; Cancer therapies; Care and treatment; Cell culture; Cell death; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Experiments; Metastases; Metastasis; Neuroendocrine tumors; Patients; Peptides; Plasma; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Radiation; Radiation therapy; Radiosensitization; Tumors; Xenografts; Netherlands; Germany; Poly(ADP-ribose)-polymerase inhibition; peptide receptor radionuclide therapy; olaparib; radiosensitization
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15030915

Peptide receptor radionuclide therapy (PRRT), a form of internal targeted radiation treatment using [ Lu]Lu [DOTA -Tyr ]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.