Abstract
Disruption of DNA damage response mechanisms can lead to replicative and transcriptional stress, accumulation of mutations and cytosolic DNA and even cell death. They can also result in malignant transformation, leading to development of breast, ovarian, colorectal, gastric or pancreatic cancer. Regulation of DNA repair processes, however, has applications in cancer therapy through activation of both the body's innate and adaptive immune response. This paper addresses the cGAS-STING system, which plays a key role in the detection of cytosolic DNA, the use of DNA repair element inhibitors (PARPi) in cancer therapy, and provides an overview of the activation of the anti-cancer response related to repair mechanisms such as homologous recombination.
References
Bednarski, Jeffrey J., and Barry P. Sleckman. 2019. ‘At the Intersection of DNA Damage and Immune Responses’. Nature Reviews. Immunology 19 (4): 231–42. https://doi.org/10.1038/s41577-019-0135-6.
Carusillo, Antonio, and Claudio Mussolino. 2020. ‘DNA Damage: From Threat to Treatment’. Cells 9 (7): 1665. https://doi.org/10.3390/cells9071665.
Chang, Howard H. Y., Nicholas R. Pannunzio, Noritaka Adachi, and Michael R. Lieber. 2017. ‘Non-Homologous DNA End Joining and Alternative Pathways to Double-Strand Break Repair’. Nature Reviews Molecular Cell Biology 18 (8): 495–506. https://doi.org/10.1038/nrm.2017.48.
Cleary, James M., Andrew J. Aguirre, Geoffrey I. Shapiro, and Alan D. D’Andrea. 2020. ‘Biomarker-Guided Development of DNA Repair Inhibitors’. Molecular Cell 78 (6): 1070–85. https://doi.org/10.1016/j.molcel.2020.04.035.
Condeelis, John, and Jeffrey W. Pollard. 2006. ‘Macrophages: Obligate Partners for Tumor Cell Migration, Invasion, and Metastasis’. Cell 124 (2): 263–66. https://doi.org/10.1016/j.cell.2006.01.007.
Corrales, Leticia, Vyara Matson, Blake Flood, Stefani Spranger, and Thomas F Gajewski. 2017. ‘Innate Immune Signaling and Regulation in Cancer Immunotherapy’. Cell Research 27 (1): 96–108. https://doi.org/10.1038/cr.2016.149.
Domchek, Susan M, Sophie Postel-Vinay, Seock-Ah Im, Yeon Hee Park, Jean-Pierre Delord, Antoine Italiano, Jerome Alexandre, et al. 2020. ‘Olaparib and Durvalumab in Patients with Germline BRCA-Mutated Metastatic Breast Cancer (MEDIOLA): An Open-Label, Multicentre, Phase 1/2, Basket Study’. The Lancet Oncology 21 (9): 1155–64. https://doi.org/10.1016/S1470-2045(20)30324-7.
Finch, Caleb E., and Eileen M. Crimmins. 2004. ‘Inflammatory Exposure and Historical Changes in Human Life-Spans’. Science 305 (5691): 1736–39. https://doi.org/10.1126/science.1092556.
González-Martín, Antonio, Bhavana Pothuri, Ignace Vergote, René DePont Christensen, Whitney Graybill, Mansoor R. Mirza, Colleen McCormick, et al. 2019. ‘Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer’. New England Journal of Medicine 381 (25): 2391–2402. https://doi.org/10.1056/NEJMoa1910962.
Grivennikov, Sergei I., Florian R. Greten, and Michael Karin. 2010. ‘Immunity, Inflammation, and Cancer’. Cell 140 (6): 883–99. https://doi.org/10.1016/j.cell.2010.01.025.
Gubin, Matthew M., Xiuli Zhang, Heiko Schuster, Etienne Caron, Jeffrey P. Ward, Takuro Noguchi, Yulia Ivanova, et al. 2014. ‘Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens’. Nature 515 (7528): 577–81. https://doi.org/10.1038/nature13988.
Hanahan, Douglas, and Robert A. Weinberg. 2011. ‘Hallmarks of Cancer: The Next Generation’. Cell 144 (5): 646–74. https://doi.org/10.1016/j.cell.2011.02.013.
Helmink, Beth A., and Barry P. Sleckman. 2012. ‘The Response to and Repair of RAG-Mediated DNA Double-Strand Breaks’. Annual Review of Immunology 30 (1): 175–202. https://doi.org/10.1146/annurev-immunol-030409-101320.
Hibino, Sana, Tetsuro Kawazoe, Hidenori Kasahara, Shinji Itoh, Takatsugu Ishimoto, Mamiko Sakata-Yanagimoto, and Koji Taniguchi. 2021. ‘Inflammation-Induced Tumorigenesis and Metastasis’. International Journal of Molecular Sciences 22 (11): 5421. https://doi.org/10.3390/ijms22115421.
Huang, Rui-Xue, and Ping-Kun Zhou. 2020. ‘DNA Damage Response Signaling Pathways and Targets for Radiotherapy Sensitization in Cancer’. Signal Transduction and Targeted Therapy 5 (1): 60. https://doi.org/10.1038/s41392-020-0150-x.
Ishikawa, Hiroki, Zhe Ma, and Glen N. Barber. 2009. ‘STING Regulates Intracellular DNA-Mediated, Type I Interferon-Dependent Innate Immunity’. Nature 461 (7265): 788–92. https://doi.org/10.1038/nature08476.
Karin, Michael, Toby Lawrence, and Victor Nizet. 2006. ‘Innate Immunity Gone Awry: Linking Microbial Infections to Chronic Inflammation and Cancer’. Cell 124 (4): 823–35. https://doi.org/10.1016/j.cell.2006.02.016.
Koole, Wouter, Robin van Schendel, Andrea E. Karambelas, Jane T. van Heteren, Kristy L. Okihara, and Marcel Tijsterman. 2014. ‘A Polymerase Theta-Dependent Repair Pathway Suppresses Extensive Genomic Instability at Endogenous G4 DNA Sites’. Nature Communications 5 (1): 3216. https://doi.org/10.1038/ncomms4216.
Kowalczykowski, Stephen C. 2015. ‘An Overview of the Molecular Mechanisms of Recombinational DNA Repair’. Cold Spring Harbor Perspectives in Biology 7 (11): a016410. https://doi.org/10.1101/cshperspect.a016410.
Li, He, Zhao-Yi Liu, Nayiyuan Wu, Yong-Chang Chen, Quan Cheng, and Jing Wang. 2020. ‘PARP Inhibitor Resistance: The Underlying Mechanisms and Clinical Implications’. Molecular Cancer 19 (1): 107. https://doi.org/10.1186/s12943-020-01227-0.
Li, Xinyi, Yichun Bai, Xinzhen Cheng, Peter Girgis Tawfek Kalds, Bing Sun, Yun Wu, Huijiao Lv, Kun Xu, and Zhiying Zhang. 2018. ‘Efficient SSA ‐mediated Precise Genome Editing Using CRISPR /Cas9’. The FEBS Journal 285 (18): 3362–75. https://doi.org/10.1111/febs.14626.
Meek, Katheryn. 2020. ‘An Antiviral DNA Response without the STING?’ Trends in Immunology 41 (5): 362–64. https://doi.org/10.1016/j.it.2020.03.010.
Mersch, Jacqueline, Michelle A. Jackson, Minjeong Park, Denise Nebgen, Susan K. Peterson, Claire Singletary, Banu K. Arun, and Jennifer K. Litton. 2015. ‘Cancers Associated with BRCA 1 and BRCA 2 Mutations Other than Breast and Ovarian: BRCA and Other Cancers’. Cancer 121 (2): 269–75. https://doi.org/10.1002/cncr.29041.
Noy, Roy, and Jeffrey W. Pollard. 2014. ‘Tumor-Associated Macrophages: From Mechanisms to Therapy’. Immunity 41 (1): 49–61. https://doi.org/10.1016/j.immuni.2014.06.010.
Park, Eek Joong, Jun Hee Lee, Guann-Yi Yu, Guobin He, Syed Raza Ali, Ryan G. Holzer, Christoph H. Österreicher, Hiroyuki Takahashi, and Michael Karin. 2010. ‘Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression’. Cell 140 (2): 197–208. https://doi.org/10.1016/j.cell.2009.12.052.
Pearl, Laurence H., Amanda C. Schierz, Simon E. Ward, Bissan Al-Lazikani, and Frances M. G. Pearl. 2015. ‘Therapeutic Opportunities within the DNA Damage Response’. Nature Reviews Cancer 15 (3): 166–80. https://doi.org/10.1038/nrc3891.
Pilger, Domenic, Leonard W. Seymour, and Stephen P. Jackson. 2021. ‘Interfaces between Cellular Responses to DNA Damage and Cancer Immunotherapy’. Genes & Development 35 (9–10): 602–18. https://doi.org/10.1101/gad.348314.121.
Pilié, Patrick G., Chad Tang, Gordon B. Mills, and Timothy A. Yap. 2019. ‘State-of-the-Art Strategies for Targeting the DNA Damage Response in Cancer’. Nature Reviews Clinical Oncology 16 (2): 81–104. https://doi.org/10.1038/s41571-018-0114-z.
Punturieri, A., E. Szabo, T. L. Croxton, S. D. Shapiro, and S. M. Dubinett. 2009. ‘Lung Cancer and Chronic Obstructive Pulmonary Disease: Needs and Opportunities for Integrated Research’. JNCI Journal of the National Cancer Institute 101 (8): 554–59. https://doi.org/10.1093/jnci/djp023.
Reisländer, Timo, Florian J. Groelly, and Madalena Tarsounas. 2020. ‘DNA Damage and Cancer Immunotherapy: A STING in the Tale’. Molecular Cell 80 (1): 21–28. https://doi.org/10.1016/j.molcel.2020.07.026.
Rodier, Francis, Jean-Philippe Coppé, Christopher K. Patil, Wieteke A. M. Hoeijmakers, Denise P. Muñoz, Saba R. Raza, Adam Freund, Eric Campeau, Albert R. Davalos, and Judith Campisi. 2009. ‘Persistent DNA Damage Signalling Triggers Senescence-Associated Inflammatory Cytokine Secretion’. Nature Cell Biology 11 (8): 973–79. https://doi.org/10.1038/ncb1909.
Scully, Ralph, Arvind Panday, Rajula Elango, and Nicholas A. Willis. 2019. ‘DNA Double-Strand Break Repair-Pathway Choice in Somatic Mammalian Cells’. Nature Reviews Molecular Cell Biology 20 (11): 698–714. https://doi.org/10.1038/s41580-019-0152-0.
Shen, Yu J., Nina Le Bert, Anuja A. Chitre, Christine Xing’Er Koo, Xing H. Nga, Samantha S.W. Ho, Muznah Khatoo, Nikki Y. Tan, Ken J. Ishii, and Stephan Gasser. 2015. ‘Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells’. Cell Reports 11 (3): 460–73. https://doi.org/10.1016/j.celrep.2015.03.041.
Stratigopoulou, Maria, Tijmen P. van Dam, and Jeroen E. J. Guikema. 2020. ‘Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences’. Frontiers in Immunology 11 (May): 1084. https://doi.org/10.3389/fimmu.2020.01084.
Sun, L., J. Wu, F. Du, X. Chen, and Z. J. Chen. 2013. ‘Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway’. Science 339 (6121): 786–91. https://doi.org/10.1126/science.1232458.
Vanpouille-Box, Claire, Sandra Demaria, Silvia C. Formenti, and Lorenzo Galluzzi. 2018. ‘Cytosolic DNA Sensing in Organismal Tumor Control’. Cancer Cell 34 (3): 361–78. https://doi.org/10.1016/j.ccell.2018.05.013.
Visser, Karin E. de, Alexandra Eichten, and Lisa M. Coussens. 2006. ‘Paradoxical Roles of the Immune System during Cancer Development’. Nature Reviews Cancer 6 (1): 24–37. https://doi.org/10.1038/nrc1782.
Wang, Manni, Siyuan Chen, and Danyi Ao. 2021. ‘Targeting DNA Repair Pathway in Cancer: Mechanisms and Clinical Application’. MedComm 2 (4): 654–91. https://doi.org/10.1002/mco2.103.
Wischnewski, Marilena, and Andrea Ablasser. 2021. ‘Interplay of CGAS with Chromatin’. Trends in Biochemical Sciences 46 (10): 822–31. https://doi.org/10.1016/j.tibs.2021.05.011.
Wu, J., L. Sun, X. Chen, F. Du, H. Shi, C. Chen, and Z. J. Chen. 2013. ‘Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA’. Science 339 (6121): 826–30. https://doi.org/10.1126/science.1229963.
Wu, Shaoguang, Ki-Jong Rhee, Emilia Albesiano, Shervin Rabizadeh, Xinqun Wu, Hung-Rong Yen, David L Huso, et al. 2009. ‘A Human Colonic Commensal Promotes Colon Tumorigenesis via Activation of T Helper Type 17 T Cell Responses’. Nature Medicine 15 (9): 1016–22. https://doi.org/10.1038/nm.2015.
Ye, Zu, Yin Shi, Susan P. Lees-Miller, and John A. Tainer. 2021. ‘Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy’. Frontiers in Immunology 12 (December): 797880. https://doi.org/10.3389/fimmu.2021.797880.
Zamarron, Brian F., and WanJun Chen. 2011. ‘Dual Roles of Immune Cells and Their Factors in Cancer Development and Progression’. International Journal of Biological Sciences 7 (5): 651–58. https://doi.org/10.7150/ijbs.7.651.
Zhu, Yuanyuan, Xiang An, Xiao Zhang, Yu Qiao, Tongsen Zheng, and Xiaobo Li. 2019. ‘STING: A Master Regulator in the Cancer-Immunity Cycle’. Molecular Cancer 18 (1): 152. https://doi.org/10.1186/s12943-019-1087-y.
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