Novel Therapeutic Approaches with DNA Damage Response Inhibitors for Melanoma Treatment
Abstract
:1. Introduction
2. Melanoma
Homologous Recombination and Melanoma
3. Targeted Therapy and Immunotherapy in Melanoma
4. DDR Inhibitors in Melanoma
4.1. PARP Inhibitors in Melanoma
4.2. ATM Inhibitors in Melanoma
4.3. CHK1 Inhibitors in Melanoma
4.4. WEE1 Inhibitors in Melanoma
4.5. ATR Inhibitors in Melanoma
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AKT | Protein kinase B |
ATM | Ataxia-telangiectasia mutated |
ATR | Ataxia-telangiectasia and Rad3-related |
ATRIP | ATR-interacting protein |
BAP1 | BRCA1-Associated Protein 1 |
BER | Base excision repair |
BET | Bromo- and Extra-Terminal Domain |
BRCA1 | Breast cancer gene 1 |
BRCA2 | Breast cancer gene 2 |
CDK | Cyclin dependent kinase |
CDKN2A | Cyclin-dependent kinase inhibitor 2A |
CHK1 | Checkpoint kinase 1 |
CHK2 | Checkpoint kinase 2 |
CTLA-4 | Cytotoxic T lymphocyte-associated protein 4 |
DCR | Disease control rate |
DDR | DNA damage response |
DSB | Double stand break |
FANCA | Fanconi anemia complementation group A |
HIF-1a | Hypoxia-inducible transcription factor 1a |
HR | Homologous recombination |
HRD | Homologous recombination deficiency |
ICI | Immune checkpoint inhibitors |
MAPK | Mitogen-activated protein kinase |
MHC | Major histocompatibility complex |
MM | Metastatic melanomas |
MMR | Mismatch repair |
MRN | MRE11–RAD50–NBS1 |
NER | Nucleotide excision repair |
NHEJ | Non-homologous-end-joining |
ORR | Overall response rate |
OS | Overall survival |
PARP | Poly (ADP-ribose) polymerase |
PD-1 | Programmed death 1 |
PD-L1 | Programmed death ligand 1 |
PDX | Patient derived xenograft |
PFS | Progression-free survival |
PTEN | Phosphatase and tensin homolog |
RPA | Replication protein A |
RTK | Receptor tyrosine kinase |
SSB | Single stand break |
SWI/SNF | Switch/sucrose non-fermentable |
TCR | T-cell receptor |
TERT | Telomerase reverse-transcriptase |
TMB | Tumor mutational burden |
UV | Ultraviolet |
VEGF | Vascular endothelial growth factor |
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Target | Compound Name | Reference |
---|---|---|
PARP | Veliparib | [62] |
Olaparib | [34,64,65,66] | |
Niraparib | [34,67] | |
Talazoparib | [67] | |
AZD2461 | [63] | |
ATM | AZD1390 | [68] |
CHK1 | AZD-7762 | [69,70,71,72] |
PF-477736 | [73] | |
AR-323, AR-678 | [74] | |
GDC-0575 | [75,76,77] | |
GNE-323 | [76] | |
SRA-737 | [77] | |
CHIR-124 | [71,78] | |
WEE1 | PD0166285 | [79] |
WEE1 inhibitor II | [78] | |
Adavosertib (AZD-1775) | [69,71,80,81,82,83,84] | |
ATR | Ceralasertib (AZD-6738) | [65,85] |
DDR Target | Agents | Phase | Trial ID * |
---|---|---|---|
PARP | Niraparib | II | NCT03925350 |
Niraparib | II | NCT05169437 | |
Niraparib | II | NCT03207347 | |
Olaparib + Pembrolizumab | II | NCT04633902 | |
Talazoparib + Nivolumab | II | NCT04187833 | |
Veliparib + Paclitaxel + Carboplatin | I | NCT01366144 | |
WEE1 | Adavosertib ZN-c3 | II I | NCT02465060 NCT04158336 |
ATR | Ceralasertib + paclitaxel | I | NCT02630199 |
Ceralasertib + durvalumab | II | NCT03780608 |
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Maresca, L.; Stecca, B.; Carrassa, L. Novel Therapeutic Approaches with DNA Damage Response Inhibitors for Melanoma Treatment. Cells 2022, 11, 1466. https://doi.org/10.3390/cells11091466
Maresca L, Stecca B, Carrassa L. Novel Therapeutic Approaches with DNA Damage Response Inhibitors for Melanoma Treatment. Cells. 2022; 11(9):1466. https://doi.org/10.3390/cells11091466
Chicago/Turabian StyleMaresca, Luisa, Barbara Stecca, and Laura Carrassa. 2022. "Novel Therapeutic Approaches with DNA Damage Response Inhibitors for Melanoma Treatment" Cells 11, no. 9: 1466. https://doi.org/10.3390/cells11091466