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34097104"],"award-info":[{"award-number":["MVTS 34097104"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Resistance to chemo- and radiotherapy is a common event among cancer patients and a reason why new cancer therapies and therapeutic strategies need to be in continuous investigation and development. DNA damage response (DDR) comprises several pathways that eliminate DNA damage to maintain genomic stability and integrity, but different types of cancers are associated with DDR machinery defects. Many improvements have been made in recent years, providing several drugs and therapeutic strategies for cancer patients, including those targeting the DDR pathways. Currently, poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) are the DDR inhibitors (DDRi) approved for several cancers, including breast, ovarian, pancreatic, and prostate cancer. However, PARPi resistance is a growing issue in clinical settings that increases disease relapse and aggravate patients\u2019 prognosis. Additionally, resistance to other DDRi is also being found and investigated. The resistance mechanisms to DDRi include reversion mutations, epigenetic modification, stabilization of the replication fork, and increased drug efflux. This review highlights the DDR pathways in cancer therapy, its role in the resistance to conventional treatments, and its exploitation for anticancer treatment. Biomarkers of treatment response, combination strategies with other anticancer agents, resistance mechanisms, and liabilities of treatment with DDR inhibitors are also discussed.<\/jats:p>","DOI":"10.3390\/ijms232314672","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T05:35:08Z","timestamp":1669268108000},"page":"14672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities"],"prefix":"10.3390","volume":"23","author":[{"given":"Dana","family":"Jurkovicova","sequence":"first","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, v.v.i. of the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-2888","authenticated-orcid":false,"given":"Christiana M.","family":"Neophytou","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2000-8950","authenticated-orcid":false,"given":"Ana \u010cipak","family":"Ga\u0161parovi\u0107","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, HR-10000 Zagreb, Croatia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-4802","authenticated-orcid":false,"given":"Ana Cristina","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Group of Environment Genetics and Oncobiology (CIMAGO), Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1056\/NEJMra0804615","article-title":"DNA Damage, Aging, and Cancer","volume":"361","author":"Hoeijmakers","year":"2009","journal-title":"N. 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