{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:24:12Z","timestamp":1786947852690,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:sec>\n                    <jats:title>Background\/objectives<\/jats:title>\n                    <jats:p>Transdermal fentanyl (TDF) is widely used for moderate-to-severe cancer pain, yet substantial variability in fentanyl exposure, analgesic response, and tolerability remains incompletely explained by clinical factors. We evaluated whether pharmacogenetic variability is associated with pharmacokinetic parameters and clinical outcomes in cancer patients receiving TDF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective, single-center study, adults with solid or hematological malignancies and chronic cancer pain treated with stable-dose 72\u2005h TDF were enrolled. Blood samples were collected for pharmacokinetic and pharmacogenetic analyses. Serum fentanyl concentrations were quantified using validated gas chromatography\u2013mass spectrometry, and AUC, C\n                      <jats:sub>max<\/jats:sub>\n                      , and t\n                      <jats:sub>max<\/jats:sub>\n                      were calculated using non-compartmental analysis. Genotyping was performed using a predefined pharmacogenetic panel. Analgesic response was defined as a \u22652-point reduction in Numeric Rating Scale score or score\u2009=\u20090 at 72\u2005h. Statistical analyses included correction for multiple testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      49 patients were included (median age 65 years; 98% stage IV disease); 38 (77.5%) were responders. No significant differences in AUC, C\n                      <jats:sub>max<\/jats:sub>\n                      , or t\n                      <jats:sub>max<\/jats:sub>\n                      were observed between responders and non-responders. TPMT and UGT2B7 variants showed unadjusted associations with clinical response and pharmacokinetic parameters, respectively; however, none remained statistically significant after correction for multiple testing. No significant associations were observed for CYP3A4\/5 or ABCB1 variants, nor between genetic variants and adverse events. Pain reduction correlated with improved functional outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this exploratory cohort, pharmacogenetic variability was not robustly associated with TDF pharmacokinetics, analgesic response, or tolerability after correction for multiple testing. These findings do not support the current clinical implementation of pharmacogenetic-guided TDF therapy, but provide hypothesis-generating signals for future studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpain.2026.1834786","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:25:45Z","timestamp":1786944345000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of genetic polymorphisms on the response to transdermal fentanyl in cancer patients\u2014a single-center, prospective, biological study"],"prefix":"10.3389","volume":"7","author":[{"given":"Lucia","family":"Angelini","sequence":"first","affiliation":[{"name":"Palliative Care Unit, IRCCS \"Istituto Romagnolo Per Lo Studio Dei Tumori (IRST), Dino Amadori\"","place":["Meldola, FC, 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