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
Department of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Cancers (Basel). 2023 Feb 1;15(3):915. 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.
肽受体放射性核素治疗（PRRT）是一种使用[镥]镥[DOTA-酪氨酸]奥曲肽的体内靶向放射治疗形式，用于治疗转移性神经内分泌肿瘤（NETs）患者。尽管PRRT现在是转移性NETs患者的二线治疗方法，但大多数患者无法通过该治疗治愈。PRRT通过放射性衰变诱导DNA损伤发挥作用，因此抑制DNA损伤修复蛋白可作为增强PRRT的一种策略。先前的研究在细胞系和小鼠中显示了PRRT与PARP抑制剂奥拉帕利联合使用的有前景的结果，我们已经采取下一步措施，使用两种不同的异种移植小鼠模型进行进一步的体内验证。我们观察到这种联合治疗仅在一种模型中提高了治疗效果，而在另一种模型中则没有。总体而言，我们的研究结果表明，PRRT和奥拉帕利联合治疗的抗肿瘤反应具有肿瘤类型依赖性。这些数据强调了对肿瘤进行分子分层以预先确定PARP抑制与PRRT联合的潜在临床价值的未满足需求。
