Targeting DNA Damage Response in Prostate and Breast Cancer
Abstract
:1. Introduction
2. DDR and Steroid Hormone Receptor Pathways
2.1. General Aspects
2.2. Transcription-Coupled DNA Repair
2.3. Cross-Talk between the AR and the DDR Pathways
2.4. Cross-Talk between the ERα and the DDR Pathways
3. Targeting the DDR for Treatment of Prostate and Breast Cancer
3.1. PARP-1 Inhibitors
3.2. DNA-PKcs Inhibitors
3.3. ATR Inhibitors
3.4. ATM Inhibitors
3.5. CHK1 Inhibitors
3.6. WEE1 Inhibitors
3.7. CDK12 Inhibitors
4. Blocking DNA Repair in Prostate and Breast Cancer to Improve Chemotherapy, General Radiation, and Targeted Radiation Therapy
5. Conclusions and Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | Additional Treatment | Condition | Inclusion Criteria | Phase | Identifier |
---|---|---|---|---|---|
Olaparib | Pembroli-zumab | Prostatic neoplasms | 3 | NCT03834519 | |
Olaparib | Cediranib | mCRPC | 2 | NCT02893917 | |
Olaparib | AZD6738 | mCRPC | 2 | NCT03787680 | |
Olaparib | Durvalumab | Castration-sensitive nmPC | DDR mutations | 2 | NCT03810105 |
Olaparib | Radium-223 | mCRPC | Bone metastases | 1/2 | NCT03317392 |
Rucaparib | mCRPC | HR deficiency | 3 | NCT02975934 | |
Rucaparib | Enzalutamide | mCRPC | Resistance to testosterone deprivation | 3 | NCT04455750 |
Rucaparib | mCRPC | HR deficiency Post-docetaxel and carboplatin | 2 | NCT03442556 | |
Rucaparib | Non-metastatic prostate cancer | BRCAness genotype | 2 | NCT03533946 | |
Niraparib | mCRPC | DNA repair anomalies | 2 | NCT02854436 | |
Niraparib | Abiraterone, leuprolide, radiotherapy | High-risk and node-positive prostate cancer | ½ | NCT04194554 | |
Veliparib | Abiraterone | mCRPC | 2 | NCT01576172 | |
Olaparib | mBC | Germline BRCA positive | 3 | NCT02000622 | |
Olaparib | Platinum-based neoadjuvant chemotherapy | TNBC | Germline BRCA positive | 2/3 | NCT03150576 |
Niraparib | TNBC | HER2 negative Germline BRCA positive | 3 | NCT01905592 | |
Veliparib | Carboplatin Paclitaxel | mBC | HER2 negative | 3 | NCT02163694 |
Talazoparib | mBC | BRCA mutation | 3 | NCT01945775 |
Compound | Target | Additional Treatment | Condition | Inclusion Criteria | Phase | Identifier |
---|---|---|---|---|---|---|
Nedisertib | DNA-PKcs | Radium-223 Avemulab | mCRPC | 1/2 | NCT04071236 | |
AZD7648 | DNA-PKcs | Doxorubicin Olaparib | Advanced cancers | 1/2 | NCT03907969 | |
VX-984 | DNA-PKcs | Chemotherapy | Advanced solid tumors | 1 | NCT02644278 | |
CC-115 | DNA-PKcs | Enzalutamide | CRPC | 1 | NCT02833883 | |
Berzosertib | ATR | Radiation therapy | Breast cancer | 1 | NCT04052555 | |
Berzosertib | ATR | Carboplatin | mCRPC | 2 | NCT03517969 | |
Ceralasertib | ATR | Olaparib | mCRPC | 2 | NCT03787680 | |
Ceralasertib | ATR | Olaparib | TNBC | 2 | NCT03330847 | |
Ceralasertib | ATR | Olaparib | Advanced breast cancer | Germline BRCA mutation | 2 | NCT04090567 |
M4344 | ATR | Chemotherapy | Advanced solid tumors | 1 | NCT02278250 | |
BAY 1895344 | ATR | Advanced solid tumors and lymphomas | 1 | NCT03188965 | ||
BAY 1895344 | ATR | Chemotherapy | Advanced solid tumors | 1 | NCT04491942 | |
BAY 1895344 | ATR | Niraparib | Advanced solid tumors | 1 | NCT04267939 | |
BAY 1895344 | ATR | Pembrolizumab | Advanced solid tumors | 1 | NCT04095273 | |
AZD0156 | ATM | Olaparib Irinotecan Fluorouracil Folinic acid | Advanced cancer | 1 | NCT02588105 | |
M3541 | ATM | Radiotherapy | Solid tumors | 1 | NCT03225105 |
Compound | Target | Additional Treatment | Condition | Inclusion Criteria | Phase | Identifier |
---|---|---|---|---|---|---|
Prexasertib | CHK1 | mCRPC TNBC Ovarian cancer | BRCA mutation | 2 | NCT02203513 | |
Prexasertib | CHK1 | LY3023414 | TNBC | 1 | NCT04032080 | |
LY2880070 | CHK1 | Gemcitabine | Solid tumors | 1 | NCT02632448 | |
Adavosertib | WEE1 | Prostate cancer | 2 | NCT03385655 | ||
Adavosertib | WEE1 | Olaparib | TNBC | 2 | NCT03330847 | |
AZD1775 | WEE1 | Cisplatin | TNBC | 2 | NCT03012477 |
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Wengner, A.M.; Scholz, A.; Haendler, B. Targeting DNA Damage Response in Prostate and Breast Cancer. Int. J. Mol. Sci. 2020, 21, 8273. https://doi.org/10.3390/ijms21218273
Wengner AM, Scholz A, Haendler B. Targeting DNA Damage Response in Prostate and Breast Cancer. International Journal of Molecular Sciences. 2020; 21(21):8273. https://doi.org/10.3390/ijms21218273
Chicago/Turabian StyleWengner, Antje M., Arne Scholz, and Bernard Haendler. 2020. "Targeting DNA Damage Response in Prostate and Breast Cancer" International Journal of Molecular Sciences 21, no. 21: 8273. https://doi.org/10.3390/ijms21218273