{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:44:39Z","timestamp":1791902679418,"version":"4.3.4"},"reference-count":103,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nitric oxide (NO), the first gaseous molecule identified as a signaling mediator, plays a pivotal role in numerous physiological processes including cardiovascular regulation, immune response, and neurotransmission. Synthesized from L-arginine by nitric oxide synthase (NOS), NO exerts both protective and cytotoxic effects depending on its local concentration. At low levels, NO supports tumor growth by mitigating oxidative stress, while at high concentrations, it induces apoptosis through mechanisms such as p53 activation, cytochrome c release, and peroxynitrite formation. These dual properties position NO as a complex but promising agent in cancer therapy. Recent studies have highlighted the potential of NO in enhancing the efficacy of photodynamic therapy (PDT), where it synergizes with reactive oxygen species (ROS) to induce cytotoxic effects in tumor cells. Despite its promise, challenges such as rapid diffusion and limited tumor accumulation hinder NO\u2019s therapeutic utility. This has spurred the development of NO donors and nanotechnology-based delivery systems to enable controlled, site-specific release. Moreover, NO has been shown to counteract multidrug resistance, improve tumor perfusion by dilating vasculature, and potentiate ROS-based therapies like PDT and radiotherapy. However, an emerging concern is NO\u2019s role in promoting proliferation and migration of non-targeted \u201cbystander\u201d tumor cells following PDT-induced stress, primarily through iNOS upregulation. This feedback loop can contribute to tumor aggressiveness and metastasis, underscoring the need for a deeper understanding of NO\u2019s molecular actions. While iNOS inhibitors show preclinical promise in various inflammatory and neoplastic conditions, no such agents have reached clinical approval, due to the complexity and context-dependent effects of NO. Future research should focus on refining NO delivery systems, developing selective iNOS inhibitors, and elucidating NO\u2019s dual role in cancer biology to fully harness its therapeutic potential in PDT and beyond.<\/jats:p>","DOI":"10.3390\/molecules30132802","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T11:37:51Z","timestamp":1751283471000},"page":"2802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Role of Nitric Oxide in Cancer Treatment: Ally or Foe?"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0658-5471","authenticated-orcid":false,"given":"Angelika","family":"My\u015bliwiec","sequence":"first","affiliation":[{"name":"Department of Biochemistry and General Chemistry, Medical Faculty, Collegium Medicum, University of Rzesz\u00f3w, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-5464","authenticated-orcid":false,"given":"Dorota","family":"Bartusik-Aebisher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and General Chemistry, Medical Faculty, Collegium Medicum, University of Rzesz\u00f3w, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2661-6570","authenticated-orcid":false,"given":"David","family":"Aebisher","sequence":"additional","affiliation":[{"name":"Department of Photomedicine and Physical Chemistry, Medical Faculty, Collegium Medicum, University of Rzesz\u00f3w, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"ref_1","first-page":"254","article-title":"Udzia\u0142 tlenku azotu w regulacji ekspresji gen\u00f3w [Regulation of gene expression by nitric oxide]","volume":"53","author":"Oszajca","year":"2007","journal-title":"Postepy Biochem."},{"key":"ref_2","first-page":"889","article-title":"Metabolizm tlenku azotu [Nitric oxide metabolism]","volume":"59","author":"Kowalczyk","year":"2006","journal-title":"Wiad. 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