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Restoring physiological normoxia as an adjuvant strategy to improve cancer treatment outcomes

dc.contributor.authorBermejo, Carlos Mas
dc.contributor.authorGómez, Carlos Mas
dc.contributor.authorSevilla-García, Ma-Agustina
dc.contributor.authorO’Connor-Reina, Carlos
dc.contributor.authorRamos, Susana Falardo
dc.contributor.authorAlonso-Romero, José Luis
dc.contributor.authorBravo-González, Luis-Alberto
dc.date.accessioned2026-06-05T16:20:33Z
dc.date.available2026-06-05T16:20:33Z
dc.date.issued2026-05-19
dc.description.abstractHypoxia is a central driver of cancer progression, immune evasion, and resistance to anticancer therapies. While hypoxia has traditionally been considered an intrinsic feature of the tumor microenvironment, growing evidence indicates that chronic intermittent hypoxia—particularly that occurring during sleep—represents a systemic and potentially modifiable contributor to hypoxia-driven oncogenic signaling. Sleep-disordered breathing is the most prevalent cause of nocturnal intermittent hypoxia and induces oxidative stress, inflammation, metabolic reprogramming, and immune dysregulation through mechanisms that overlap with those observed in hypoxic tumors.This narrative review synthesizes current experimental, translational, and clinical evidence supporting the concept that restoration of physiological normoxia, especially during sleep, may attenuate hypoxia-mediated cancer biology and improve responsiveness to standard anticancer therapies. We examine the biological effects of normoxia restoration on hypoxia-inducible signaling, redox homeostasis, tumor metabolism, and antitumor immunity, highlighting its potential role as a host-directed, adjuvant strategy rather than a direct tumor-targeting intervention.We further review sleep and airway-centered therapeutic approaches capable of reducing nocturnal hypoxic burden, including continuous positive airway pressure, mandibular advancement devices, upper airway surgery, myofunctional therapy, and respiratory physiotherapy. Although these interventions are not cancer-specific, their ability to stabilize nocturnal oxygenation positions them as clinically relevant tools within a multidisciplinary framework aimed at hypoxia normalization.Collectively, the evidence suggests that nocturnal normoxia is a biologically meaningful and clinically actionable target. Integrating sleep and airway interventions into cancer care pathways may represent a novel avenue to mitigate hypoxia-driven treatment resistance and enhance therapeutic outcomes. Prospective clinical studies incorporating objective measures of hypoxic burden are warranted to validate this integrative approach.Restoration of physiological normoxia is therefore proposed as a host-directed, adjuvant strategy aimed at mitigating hypoxia-driven oncogenic pathways and improving responsiveness to standard anticancer therapies.eng
dc.identifier.doi10.2147/NSS.S593331
dc.identifier.eid105039479823
dc.identifier.other5397e457-7601-457e-9ba3-ec3a507d6f39
dc.identifier.urihttp://hdl.handle.net/10400.14/57997
dc.language.isoeng
dc.peerreviewedyes
dc.publisherDove Medical Press Ltd
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectCancereng
dc.subjectCPAPeng
dc.subjectHypoxiaeng
dc.subjectIntermittent hypoxiaeng
dc.subjectNormoxiaeng
dc.subjectSleep-disordered breathingeng
dc.subjectTreatment resistanceeng
dc.subjectUpper airway therapyeng
dc.titleRestoring physiological normoxia as an adjuvant strategy to improve cancer treatment outcomes
dc.typereview article
dspace.entity.typePublication
oaire.citation.volume18
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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