A mathematical model for the investigation of combined treatment of radiopharmaceutical therapy and PARP inhibitors

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Abstract Background Although the combined treatment with radiopharmaceutical therapy (RPT) and poly (ADP-ribose) polymerase inhibitors (PARPi) shows promise, a critical challenge remains in limited quantitative understanding needed to optimize protocols. This study introduces mathematical model that quantitatively represents homologous recombination deficiency (HRD) facilitates patient-specific customization of therapeutic schedules. Methods The predicts outcomes based on absorbed dose by DNA resulting radiobiological responses, double-strand breaks (DSBs) being determinant cancer cell fate. effect PARPi is modeled accelerated conversion single-strand (SSBs) DSBs due PARP-trapping S phase, while HRD represented defects DSB repair replicated DNA. In vitro experiments are used calibrate parameters validate model. silico tests designed extensively investigate various combination protocols including LuPARP trial. Results Model calibration was performed using data from NCI-H69 cells [ 177 Lu]Lu-DOTA-TOC PARPi. Previously published vivo studies were integrated into presented validation showed deviations within experimental error margins, average 5.3 ± 3.2% without PARPi, 6.1 4.4% Olaparib, 12 18% Rucaparib. Rucaparib radiosensitization reduces number tumor during lutetium 99.2% 99.99% (HRD). highest radiosensitizing observed Talazoparib (IC50: 4.8 nM), followed 1.4 µM). relative shrinkage after 14 days Olaparib (250 mg) patient body weight (e.g. 60 kg: 99.6%; 90 98.0%). Conclusion demonstrate potential this computational as step toward development digital twin for systematic exploration optimization clinical

Язык: Английский

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Peptide receptor radionuclide therapy with somatostatin analogs beyond gastroenteropancreatic neuroendocrine tumors

Journal of Neuroendocrinology, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Abstract First isolated by Brazeau et al. in 1972, somatostatin (SST) is a neuropeptide known for regulating various signaling pathways through its specific cell surface receptors. Somatostatin receptors (SSTRs) comprise family of five G protein‐coupled that are widely distributed across the human body and expressed tumor types. The growing understanding their clinical potential led to introduction both cold radiolabeled analogs (SSAs), which have revolutionized management several cancers, especially neuroendocrine tumors. As direct consequence, advances peptide receptor radionuclide therapy (PRRT) over last 30 years approval 177 Lu‐DOTATATE treatment gastroenteropancreatic tumors (GEPNETs). Theoretically, any cancer patients whose express SSTR, as demonstrated vivo SSTR‐based molecular imaging, could be candidates PRRT, those with limited options. However, evidence on efficacy PRRT non‐GEPNET SSTR‐expressing limited, mainly derived from small retrospective studies. Given therapeutic options advanced/metastatic patients, there clear need randomized trials formally approve SSAs who may benefit this treatment, particularly certain types neoplasms such lung carcinoids, paragangliomas, meningiomas, where high rates disease control (up 80%) can achieved. In addition, emerging supports combination therapies, alpha emitters, non‐SSTR‐based beyond GEPNET. This review aims provide comprehensive overview PRRT's role cancers GEPNET, exploring new possibilities future directions most SSTR highly expressing

Язык: Английский

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Advances with radiopharmaceutical therapy in cancer

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Enhancing Effects of Olaparib by Alpha- and Beta-Emitting Radionuclides, X-Rays, and Ultraviolet A Light in Combination with Ortho-IodoHoechst in a Prostate Cancer Cell Model

Pharmaceuticals, Год журнала: 2024, Номер 17(11), С. 1450 - 1450

Опубликована: Окт. 30, 2024

New therapeutic strategies for metastatic castration-resistant prostate cancer (mCRPC) have been developed in the past to achieve best response rates. Most recently, use of combination therapies has explored optimize patient outcomes. Poly(ADP-ribose) polymerase inhibitors (PARPi) may help treat mCRPC more effectively.

Язык: Английский

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[177Lu]Lu DOTATOC PRRT with PARP inhibitors in small cell lung cancer

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2024, Номер 52(1), С. 260 - 262

Опубликована: Авг. 27, 2024

Язык: Английский

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