Radiotherapy, PARP Inhibition, and Immune-Checkpoint Blockade: A Triad to Overcome the Double-Edged Effects of Each Single Player
Abstract
:Simple Summary
Abstract
1. Introduction
2. Radiotherapy
3. Immuno-Stimulating Effects of Radiotherapy
4. Immuno-Depressing Effects of Radiotherapy
5. PARP Inhibitors
6. Synergy between PARPi and Radiotherapy
7. Synergic Immunological Effects of RT and PARPi
8. Immune-Checkpoint Inhibitors
9. Synergy between Radiotherapy and ICI
10. Synergy between PARPi and ICI
11. Conclusions: Combining RT, PARPis, and ICIs to Overcome Respective Limitations
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Title | Conditions | Therapies | Phase | Estimated Enrollment (Patients) | Status | Estimated Completion Dates | NCT Number | Last Update Posted |
---|---|---|---|---|---|---|---|---|
Testing the safety of the anticancer drugs durvalumab and olaparib during radiation therapy for locally advanced unresectable pancreatic cancer | Locally advanced pancreatic carcinoma Stage II or III pancreatic cancer Unresectable pancreatic carcinoma | Durvalumab Olaparib RT | I | 18 | Recruiting | Primary and final: 31 March 2024 | 05411094 | 1 December 2022 |
A safety study adding niraparib and dostarlimab to radiation therapy for rectal cancers | Rectal neoplasms Rectal neoplasm malignant | Niraparib Dostarlimab Short course RT | I–II | 38 | Recruiting | Primary: 31 December 2024 Final: 31 December 2026 | 04926324 | 26 July 2022 |
Niraparib + dostarlimab + RT in pancreatic cancer | Pancreatic cancer Metastatic pancreatic cancer | Niraparib Dostarlimab RT | II | 25 | Active, not recruiting | Primary: 19 January 2022 Final: October 2026 | 04409002 | 8 September 2022 |
Radiation, immunotherapy, and PARP inhibitor in triple-negative breast cancer | Breast cancer TNBC | Niraparib Dostarlimab RT | II | 32 | Recruiting | Primary: 1 April 2023 Final: 1 December 2029 | 04837209 | 23 December 2022 |
Radiotherapy and durvalumab/durvalumab combo (tremelimumab/olaparid) for small-cell lung cancer | SCLC extensive stage SCLC | Durvalumab Tremelimumab Olaparib Thoracic RT | I | 25 | Active, not recruiting | Primary and final: 1 June 2023 | 03923270 | 6 January 2023 |
A study of radiation therapy with pembrolizumab and olaparib or other radiosensitizers in women who have triple-negative or hormone-receptor positive/HER2 negative breast cancer | TNBC Metastatic breast cancer | Pembrolizumab Olaparib RT | II | 34 | Recruiting | Primary and final: January 2025 | 04683679 | 21 October 2022 |
Pembro with radiation with or without olaparib | Prostate cancer | Pembrolizumab Olaparib Androgen deprivation therapy RT | II | 64 | Not yet recruiting | Primary: 2 January 2025 Final: 2 January 2028 | 05568550 | 5 October 2022 |
Olaparib and durvalumab with carboplatin, etoposide, and/or radiation therapy for the treatment of extensive-stage small-cell lung cancer, PRIO trial | Extensive-stage SCLC Stage IV lung cancer Stage IVA lung cancer Stage IVB lung cancer | Carboplatin Durvalumab Etoposide Olaparib RT | I–II | 63 | Recruiting | Primary and final: 31 January 2024 | 04728230 | 9 November 2022 |
Study of SBRT/olaparib followed by pembrolizumab/olaparib in gastric cancers | Gastric cancer Gastroesophageal cancer | Pembrolizumab Olaparib SBRT | II | 26 | Recruiting | Primary: December 2025 Final: December 2028 | 05379972 | 5 January 2023 |
Placebo-controlled study of concurrent chemoradiation therapy with pembrolizumab followed by pembrolizumab and olaparib in newly diagnosed treatment-naïve limited-stage small-cell lung cancer (LS-SCLC) (MK 7339-013/KEYLYNK-013) | SCLC | Pembrolizumab (2 doses) Olaparib Etoposide Platinum Standard thoracic RT Prophylactic cranial irradiation | III | 672 | Recruiting | Primary and final: 28 October 2027 | 04624204 | 23 December 2022 |
Pembrolizumab plus olaparib in LA-HNSCC | Head and neck squamous cell carcinoma | Pembrolizumab Olaparib Cisplatin IMRT | II | 45 | Recruiting | Primary: 31 October 2024 Final: 31 October 2025 | 05366166 | 28 October 2022 |
Study of pembrolizumab with concurrent chemoradiation therapy, followed by pembrolizumab with or without olaparib in stage III non-small-cell lung cancer (NSCLC) (MK-7339-012/KEYLYNK-012) | Lung neoplasms NSCLC | Pembrolizumab Olaparib Etoposide Carboplatin Cisplatin Paclitaxel Pemetrexed Thoracic RT Durvalumab | III | 870 | Recruiting | Primary and final: 6 July 2026 | 04380636 | 30 November 2022 |
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Rosado, M.M.; Pioli, C. Radiotherapy, PARP Inhibition, and Immune-Checkpoint Blockade: A Triad to Overcome the Double-Edged Effects of Each Single Player. Cancers 2023, 15, 1093. https://doi.org/10.3390/cancers15041093
Rosado MM, Pioli C. Radiotherapy, PARP Inhibition, and Immune-Checkpoint Blockade: A Triad to Overcome the Double-Edged Effects of Each Single Player. Cancers. 2023; 15(4):1093. https://doi.org/10.3390/cancers15041093
Chicago/Turabian StyleRosado, Maria Manuela, and Claudio Pioli. 2023. "Radiotherapy, PARP Inhibition, and Immune-Checkpoint Blockade: A Triad to Overcome the Double-Edged Effects of Each Single Player" Cancers 15, no. 4: 1093. https://doi.org/10.3390/cancers15041093