Conventional DNA-Damaging Cancer Therapies and Emerging cGAS-STING Activation: A Review and Perspectives Regarding Immunotherapeutic Potential
Abstract
:Simple Summary
Abstract
1. Introduction
2. Conventional Cancer Therapies and cGAS-STING Activation
2.1. Antimitotic Agents
2.2. DDR Inhibitors
2.2.1. Topoisomerase Inhibitors
2.2.2. PARP Inhibitors
2.2.3. Ataxia Telangiectasia and Rad3-Related (ATR) and ATM Inhibitors
2.2.4. RNA Polymerase Inhibitors
2.3. DNA-Damaging Agents
2.3.1. Ionizing Radiation
2.3.2. Alkylating Agents
2.3.3. Nucleoside Analogs
3. Future Perspectives
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Category | Class | Mechanism of DNA Damage | Agent | Dose | Reference |
---|---|---|---|---|---|
Antimitotic Agents | Microtubule Targeting Agents | Induction of apoptosis-associated nucleases; Disruption of intracellular DNA repair protein trafficking. | Taxol (Paclitaxel) Eribulin | Cytotoxic Cytotoxic | [94] [95] [96] [97] |
DDR Enzyme Inhibitors | Topoisomerase Inhibitors | Disruption of enzyme catalyzed changes in DNA double helix structure during replication, transcription and repair. | Camptothecin | Non-Cytotoxic | [98] |
Camptothecin + Cisplatin | Cytotoxic | [99] | |||
SN38 | Cytotoxic | [100] | |||
Topotecan | Cytotoxic | [101] | |||
Doxorubicin, Daunorubicin | Non-Cytotoxic | [102] | |||
Etoposide | Non-Cytotoxic Cytotoxic | [103] [104] | |||
PARP Inhibitors | Disruption of enzyme catalyzed synthesis of Poly(ADP-ribose) signal for other DNA-repairing enzymes. | Olaparib | Cytotoxic | [105] | |
[106] | |||||
[107] | |||||
N/A | [108] | ||||
Rucaparib | Cytotoxic | [105] | |||
Talazoparib | Non-Cytotoxic (Cytostatic) | [109] | |||
ATR and ATM Inhibitors | Indirect DNA damage from inhibition of DDR; Disruption of coordination between cell cycle and DDR. | Ceralasertib (AZD6738) KU60019 AZD1390 and KU55933 | N/A N/A N/A | [110] [111] [112] | |
RNA Polymerase Inhibitors | Nucleolar disruption from blocking of transcription initiation and promoter release. | CX-5461 | N/A | [113] | |
Direct DNA-Damaging Agents | Radiotherapy | Base pair damage, single- and double-strand breaks from high energy of radiation. | Ionizing Radiation | N/A | Reviewed in [114] |
Alkylating Agents | Covalent attachment of alkyl groups to guanine base purine rings which interferes with enzymes involved in replication and transcription. | Cisplatin | Cytotoxic | [115] [116] | |
Cisplatin + Camptothecin | Cytotoxic | [99] | |||
Carboplatin | Non-Cytotoxic | [117] | |||
Nucleoside Analogs | Disruption of cellular nucleic acid synthesis; Incorporation into DNA sequence leading to stalled replication forks. | 5-Fluorouracil | Non-Cytotoxic | [118] | |
Gemcitabine | N/A | [119] | |||
Cytarabine | Non-Cytotoxic (Cytostatic) | [120] |
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Lewicky, J.D.; Martel, A.L.; Gupta, M.R.; Roy, R.; Rodriguez, G.M.; Vanderhyden, B.C.; Le, H.-T. Conventional DNA-Damaging Cancer Therapies and Emerging cGAS-STING Activation: A Review and Perspectives Regarding Immunotherapeutic Potential. Cancers 2023, 15, 4127. https://doi.org/10.3390/cancers15164127
Lewicky JD, Martel AL, Gupta MR, Roy R, Rodriguez GM, Vanderhyden BC, Le H-T. Conventional DNA-Damaging Cancer Therapies and Emerging cGAS-STING Activation: A Review and Perspectives Regarding Immunotherapeutic Potential. Cancers. 2023; 15(16):4127. https://doi.org/10.3390/cancers15164127
Chicago/Turabian StyleLewicky, Jordan D., Alexandrine L. Martel, Mukul Raj Gupta, René Roy, Galaxia M. Rodriguez, Barbara C. Vanderhyden, and Hoang-Thanh Le. 2023. "Conventional DNA-Damaging Cancer Therapies and Emerging cGAS-STING Activation: A Review and Perspectives Regarding Immunotherapeutic Potential" Cancers 15, no. 16: 4127. https://doi.org/10.3390/cancers15164127
APA StyleLewicky, J. D., Martel, A. L., Gupta, M. R., Roy, R., Rodriguez, G. M., Vanderhyden, B. C., & Le, H. -T. (2023). Conventional DNA-Damaging Cancer Therapies and Emerging cGAS-STING Activation: A Review and Perspectives Regarding Immunotherapeutic Potential. Cancers, 15(16), 4127. https://doi.org/10.3390/cancers15164127