{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:06:06Z","timestamp":1779782766174,"version":"3.53.1"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["628564"],"award-info":[{"award-number":["628564"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Sunitinib has marked pharmacokinetic (PK) and pharmacodynamic (PD) interpatient variability. This study evaluated the utility of extensive excretory\/metabolic\/PD pharmacogenomics (PGx) with hepatic functional imaging (HNI) to explore their associations with sunitinib PK\/PD (toxicity\/response) and progression\u2010free survival (PFS), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eligible patients (pts) suitable for sunitinib therapy. At baseline: (i) PGx: blood analysed by the Affymetrix DMET\u2122 Plus Array (1936 variants\/225 genes) and Sanger sequencing (HNF1A, FLT3, VEGFR2, VEGFR3, RET, PDGFR\u03b1, TNF\u03b1). (ii) HNI: pts given IV 800\u2009MBq\n                      <jats:sup>99m<\/jats:sup>\n                      Tc\u2010MIBI, imaging data analysed for hepatic extraction\/excretion parameters (CL\n                      <jats:sub>HNI<\/jats:sub>\n                      , T\n                      <jats:sub>1\/2\u2010HNI<\/jats:sub>\n                      , 1hRET, HEF, T\n                      <jats:sub>d1\/2<\/jats:sub>\n                      ). In cycles 1 and 2, bloods taken for sunitinib parent (SU), metabolite (SU12662) and total SU (metabolite\u2009+\u2009parent) PK. Associations evaluated between (i) HNI parameters and (2) PGx, with sunitinib PK, toxicity\/response and PFS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200915 pts. The two most significant associations in either direction between PGx variants or HNI parameters (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05) for: (i) PK included: (a) SU logAUC\n                      <jats:sub>0\u201314days<\/jats:sub>\n                      with HEF, ATP7B (rs1801246) and UGT8 (rs4148254); (b) SU logAUC\n                      <jats:sub>0\u201328days<\/jats:sub>\n                      , with T\n                      <jats:sub>d1\/2<\/jats:sub>\n                      , SLC15A1 (rs8187832) and SLC10A2 (rs188096); (c) SU12662 logAUC\n                      <jats:sub>0\u201314days<\/jats:sub>\n                      with HEF, ABCC3 (rs11568591), PPARD (rs1003973) and SLC15A1 (rs8187840); and (d) SU12662 logAUC\n                      <jats:sub>0\u201328days<\/jats:sub>\n                      with SULT1A2 (rs1059491) and SLC10A2 (rs188096). (ii) Toxicity: (a) Diarrhoea grade 1+ with HEF, VEFGR3 (rs307826) and AKAP9 (rs7785971); (b) \u2265grade 3 AEs with CBR1 (rs998383); (iii) overall response rate with SULT1E1 (rs1881668) and GSTA2 (rs2180314); and (iv) PFS with CYP4Z1 (rs4926802) and CYP2A6 (rs28399442).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Exploratory associations were observed between sunitinib PK\/PD with hepatic functional imaging with extensive pharmacogenomics. Further validation is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70431","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:04:34Z","timestamp":1767571474000},"page":"1652-1665","source":"Crossref","is-referenced-by-count":0,"title":["The utility of genomics and functional imaging to predict sunitinib pharmacokinetics and pharmacodynamics: The predict SU study"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-2662","authenticated-orcid":false,"given":"Michael","family":"Michael","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Peter MacCallum Cancer Centre  Melbourne Victoria Australia"},{"name":"Sir Peter MacCallum Department of Oncology University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy C.","family":"Toner","sequence":"additional","affiliation":[{"name":"Department of Medical 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