{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:27:45Z","timestamp":1780514865763,"version":"3.54.1"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency impairs NADPH generation through the pentose phosphate pathway, resulting in reduced glutathione regeneration and increased vulnerability to oxidative stress. While its clinical significance is well described in hemolytic disorders, its impact on tumor biology and chemosensitivity remains poorly characterized. Cisplatin, a backbone agent in the management of nasopharyngeal carcinoma (NPC), exerts its cytotoxicity through the formation of DNA adducts and the robust induction of reactive oxygen species (ROS) activity. We report a patient with non-keratinizing NPC and a G6PD variant, a (class III) deficiency, who demonstrated a rapid and pronounced objective response to cisplatin-based induction and concurrent chemoradiotherapy. Unfortunately, the patient also exhibited signs of rapid and persistent hematologic (platelets and white cells) toxicity. Notably, no hemolytic events occurred. A narrative review of the available literature indicates that G6PD-deficient cells exhibit a reduced antioxidant reserve, increased cisplatin-induced DNA damage, and impaired activation of ROS-detoxifying pathways. A few clinical observations similarly report enhanced tumor responsiveness in G6PD-deficient individuals, although the evidence is sparse and heterogeneous. Preclinical data support the notion that diminished NADPH availability amplifies cisplatin-triggered oxidative injury, thereby increasing tumor susceptibility. This case adds to emerging evidence that G6PD deficiency may potentiate cisplatin efficacy in NPC by exploiting intrinsic redox vulnerabilities. While preliminary, these findings suggest the potential utility of metabolic phenotyping in treatment stratification. Prospective studies are needed to define the predictive value, safety, and therapeutic implications of G6PD status in cisplatin-based regimens.<\/jats:p>","DOI":"10.3390\/ijms27093798","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:28:23Z","timestamp":1777040903000},"page":"3798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Does Glucose-6-Phosphate Dehydrogenase Deficiency Correlate with Increased Sensitivity to Cisplatin? A Case Report and a Narrative Literature Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8605-4290","authenticated-orcid":false,"given":"Nerina","family":"Denaro","sequence":"first","affiliation":[{"name":"Medical Oncology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4051-3957","authenticated-orcid":false,"given":"Valeria","family":"Smiroldo","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Bareggi","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-8708","authenticated-orcid":false,"given":"Cinzia","family":"Solinas","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, University Hospital and University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Ghidini","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9217-3456","authenticated-orcid":false,"given":"Massimo","family":"Castellani","sequence":"additional","affiliation":[{"name":"Medicina Nucleare Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-7467","authenticated-orcid":false,"given":"Marco Carlo","family":"Merlano","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO-IRCCS Candiolo, 10060 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafina","family":"Martella","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Giossi","sequence":"additional","affiliation":[{"name":"SC Analisi Chimico Cliniche ASST Grande Ospedale Metropolitano Niguarda Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Casbarra","sequence":"additional","affiliation":[{"name":"SC Radioterapia ASST Grande Ospedale Metropolitano Niguarda Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-5410","authenticated-orcid":false,"given":"Ornella","family":"Garrone","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1182\/blood.V14.2.103.103","article-title":"The hemolytic effect of primaquine and related compounds: A Review","volume":"14","author":"Beutler","year":"1959","journal-title":"Blood"},{"key":"ref_2","unstructured":"Richardson, S.R., and O\u2019Malley, G.F. 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