{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:13:16Z","timestamp":1792120396860,"version":"4.4.0"},"reference-count":275,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Statutory Subsidy Funds of the Department of Molecular and Cellular Biology","award":["SUBZ.D260.25.027"],"award-info":[{"award-number":["SUBZ.D260.25.027"]}]},{"name":"the Statutory Subsidy Funds of the Department of Molecular and Cellular Biology","award":["148"],"award-info":[{"award-number":["148"]}]},{"name":"the Students\u2019 Research Group of Cancer Cell Biology of the Department of Molecular and Cell Biology of the Wroclaw Medical University","award":["SUBZ.D260.25.027"],"award-info":[{"award-number":["SUBZ.D260.25.027"]}]},{"name":"the Students\u2019 Research Group of Cancer Cell Biology of the Department of Molecular and Cell Biology of the Wroclaw Medical University","award":["148"],"award-info":[{"award-number":["148"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hypoxia, characterized by a reduction in tissue oxygen levels, is a hallmark of many solid tumors and affects a range of cellular processes, including DNA repair. In low-oxygen conditions, cancer cells often suppress key DNA repair pathways such as homologous recombination (HR), leading to the accumulation of DNA damage and increased genomic instability. These changes not only drive tumor progression but also contribute to resistance against conventional therapies. Hypoxia significantly reduces the effectiveness of oxygen-dependent treatments, including radiotherapy and many chemotherapeutic agents. To address this limitation, bioreductive drugs have been developed that become selectively activated in hypoxic environments, providing targeted cytotoxic effects within oxygen-deprived tumor regions. Additionally, the rapid growth of tumors often results in disorganized and inefficient vasculature, further impairing the delivery of oxygen and therapeutic agents. This review explores the molecular mechanisms by which hypoxia disrupts DNA repair and contributes to treatment resistance. It also presents emerging therapeutic strategies aimed at targeting the hypoxic tumor microenvironment to improve treatment efficacy and patient outcomes.<\/jats:p>","DOI":"10.3390\/cells14141057","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:36:58Z","timestamp":1752161818000},"page":"1057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6416-9989","authenticated-orcid":false,"given":"Dominika","family":"Kunachowicz","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Tomecka","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miko\u0142aj","family":"S\u0119dzik","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Kalinin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Ku\u017anicki","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9435-9409","authenticated-orcid":false,"given":"Nina","family":"Rembia\u0142kowska","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bigos, K.J., Quiles, C.G., Lunj, S., Smith, D.J., Krause, M., Troost, E.G., West, C.M., Hoskin, P., and Choudhury, A. 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