{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:00:16Z","timestamp":1790622016153,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008728","name":"Japan Research Foundation for Clinical Pharmacology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008728","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>In the GENESECT study, no significant gemcitabine (GEM) metabolism\u2010related germline genetic polymorphisms (GPs) were identified because approximately 70% of patients received combination therapy with nab\u2010paclitaxel, which has metabolic pathways different from GEM. The present study was a sub\u2010analysis including only GEM monotherapy patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Of 159 patients analysed in the GENESECT study, only GEM\u2010monotherapy patients were selected. The endpoints included carbohydrate antigen 19\u20109 (CA19\u20109) response (reduction \u2265\u200950% from the pretreatment level at 8\u00a0weeks), progression\u2010free survival (PFS), and overall survival (OS) in relation to GPs. Analysed genes included those encoding GEM transporters and metabolic enzymes (\n                      <jats:italic>SLC29A1<\/jats:italic>\n                      ,\n                      <jats:italic>ABCC5<\/jats:italic>\n                      ,\n                      <jats:italic>CDA<\/jats:italic>\n                      ,\n                      <jats:italic>DCK<\/jats:italic>\n                      ,\n                      <jats:italic>RRM1\/2<\/jats:italic>\n                      ) and a tumour cell proliferation enzyme (\n                      <jats:italic>COX\u20102<\/jats:italic>\n                      ). Screening and significance levels were set at 10% (univariable) and 5% (multivariable), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data for 50 patients were analysed. Genotype AA of\n                      <jats:italic>ABCC5<\/jats:italic>\n                      1146A&gt;G (rs7636910) showed a higher CA19\u20109 response rate than AG\/GG (52.9% vs. 21.2%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.023) and remained significant in multivariable analysis (odds ratio: 6.255,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014). It also tended to be associated with longer PFS, but not significantly (hazard ratio [HR]: 0.464,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.074). By contrast, although CA19\u20109 responses were not significantly associated with\n                      <jats:italic>DCK<\/jats:italic>\n                      \u22121205T&gt;C (rs4694362), the TT\/TC genotype was significantly associated with prolonged PFS compared with CC (median 127 vs. 48\u2009days,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), and this association remained significant in multivariable analysis (HR: 0.153,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.028). No GPs were significantly associated with OS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ABCC5<\/jats:italic>\n                      and\n                      <jats:italic>DCK<\/jats:italic>\n                      might be related to the efficacy of GEM treatment, but further research is needed.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70611","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T07:40:40Z","timestamp":1780299640000},"page":"3397-3406","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenomic profiling of the efficacy of gemcitabine monotherapy in metastatic pancreatic cancer: Subgroup analysis of the GENESECT study"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9988-128X","authenticated-orcid":false,"given":"Takashi","family":"Yokokawa","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy Tokyo University of Pharmacy and Life Sciences  Tokyo Japan"},{"name":"Department of Pharmacy Cancer Institute Hospital of Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8894-2841","authenticated-orcid":false,"given":"Daiki","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences University of Shizuoka  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5914-504X","authenticated-orcid":false,"given":"Masahiro","family":"Hatori","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Cancer Institute Hospital of Japanese Foundation for Cancer Research  Tokyo Japan"},{"name":"Department of Clinical Pharmacology &amp; 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