{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:12:22Z","timestamp":1780679542158,"version":"3.54.1"},"reference-count":48,"publisher":"Frontiers Media SA","issue":"11","license":[{"start":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T00:00:00Z","timestamp":1492732800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA CA168699"],"award-info":[{"award-number":["R01CA CA168699"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP130547"],"award-info":[{"award-number":["RP130547"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in\u00a0vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved &lt;10\u2009\u00b5mol\/L concentrations in patients. To improve bioavailability of 4-HPR, new oral powder (LYM-X-SORB\u00ae, LXS) and intravenous lipid emulsion (ILE) formulations are being tested in early-phase clinical trials. ILE 4-HPR administered as five-day continuous infusion achieved over 50\u2009\u00b5mol\/L at MTD with minimal systemic toxicities; multiple complete and partial responses were observed in peripheral T cell lymphomas. The LXS oral powder 4-HPR formulation increased plasma levels approximately two-fold at MTD in children without dose-limiting toxicities and demonstrated multiple complete responses in recurrent neuroblastoma. The clinical activity observed with new 4-HPR formulations is attributed to increased bioavailability. Phase I and II clinical trials of both LXS 4-HPR and ILE 4-HPR are in progress as a single agent or in combination with other drugs.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Impact statement<\/jats:title>\n                    <jats:p>One of the critical components in drug development is understanding pharmacology (especially pharmacokinetics) of the drugs being developed. Often the pharmacokinetic properties, such as poor solubility leading to poor bioavailability, of the drug can limit further development of the drug. The development of numerous drugs has often halted at clinical testing stages, and several of them were due to the pharmacological properties of the agents, resulting in increased drug development cost. The current review provides an example of how improved clinical activity can be achieved by changing the formulations of a drug with poor bioavailability. Thus, it emphasizes the importance of understanding pharmacologic characteristics of the drug in drug development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1535370217706952","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T07:20:09Z","timestamp":1492759209000},"page":"1178-1184","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":60,"title":["Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives"],"prefix":"10.3389","volume":"242","author":[{"given":"Jason P","family":"Cooper","sequence":"first","affiliation":[{"name":"Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Cell Biology & Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Divisions of Hematology and Medical Oncology, Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Patrick","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Cell Biology & Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Pharmacology & Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwangeui","family":"Cho","sequence":"additional","affiliation":[{"name":"Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Cell Biology & Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min H","family":"Kang","sequence":"additional","affiliation":[{"name":"Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Cell Biology & Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Pharmacology & Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,4,21]]},"reference":[{"key":"bibr1-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-006-9289-3"},{"key":"bibr2-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1981.tb12733.x"},{"key":"bibr3-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1980.01640270043010"},{"key":"bibr4-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8588(05)70256-2"},{"key":"bibr5-1535370217706952","first-page":"2699","volume":"36","author":"Sporn MB","year":"1976","journal-title":"Cancer Res"},{"key":"bibr6-1535370217706952","first-page":"2528","volume":"38","author":"Sporn MB","year":"1979","journal-title":"Fed Proc"},{"key":"bibr7-1535370217706952","first-page":"1339","volume":"39","author":"Moon RC","year":"1979","journal-title":"Cancer Res"},{"key":"bibr8-1535370217706952","first-page":"88","volume":"21","author":"Becci PJ","year":"1980","journal-title":"Proc Am Assoc Cancer Res"},{"key":"bibr9-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/2.11.1167"},{"key":"bibr10-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(86)90003-0"},{"key":"bibr11-1535370217706952","first-page":"6036","volume":"53","author":"Delia D","year":"1993","journal-title":"Cancer Res"},{"key":"bibr12-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/86.16.1245"},{"key":"bibr13-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/87.22.1674"},{"key":"bibr14-1535370217706952","first-page":"855","volume":"2","author":"Oridate N","year":"1996","journal-title":"Clin Cancer Res"},{"key":"bibr15-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402485"},{"key":"bibr16-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1002\/1096-911X(20001201)35:6<597::AID-MPO23>3.0.CO;2-B"},{"key":"bibr17-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.21.1847"},{"key":"bibr18-1535370217706952","first-page":"1071","volume":"9","author":"Decensi A","year":"2000","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"bibr19-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0733"},{"key":"bibr20-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20923"},{"key":"bibr21-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2636"},{"key":"bibr22-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-08-0100"},{"key":"bibr23-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-199702000-00008"},{"key":"bibr24-1535370217706952","first-page":"2032","volume":"9","author":"Garaventa A","year":"2003","journal-title":"Clin Cancer Res"},{"key":"bibr25-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.9271"},{"key":"bibr26-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0995"},{"key":"bibr27-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24643"},{"key":"bibr28-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.09.096"},{"key":"bibr29-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-005-5864-7"},{"key":"bibr30-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2007.25.18_suppl.5555"},{"key":"bibr32-1535370217706952","first-page":"7299","volume":"22","author":"Schneider BJ","year":"2004","journal-title":"ASCO Meeting Abstr"},{"key":"bibr33-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.3.474"},{"key":"bibr34-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.10.2036"},{"key":"bibr36-1535370217706952","first-page":"4769","volume":"53","author":"Torrisi R","year":"1993","journal-title":"Cancer Res"},{"key":"bibr37-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1016\/0964-1955(92)90035-Y"},{"key":"bibr38-1535370217706952","first-page":"C159","volume":"48","author":"Liu X","year":"2007","journal-title":"AACR Meeting Abstracts"},{"key":"bibr39-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1889"},{"key":"bibr40-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb12118.x"},{"key":"bibr41-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1053\/ctrv.1999.0127"},{"key":"bibr42-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1007\/BF00171846"},{"key":"bibr43-1535370217706952","first-page":"485","volume":"20","author":"Jasti BR","year":"2001","journal-title":"[abstract]. Proc Am Soc Clin Oncol"},{"key":"bibr44-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14451"},{"key":"bibr45-1535370217706952","doi-asserted-by":"publisher","DOI":"10.3816\/CGC.2009.n.008"},{"key":"bibr46-1535370217706952","first-page":"5374","volume":"53","author":"Formelli F","year":"1993","journal-title":"Cancer Res"},{"key":"bibr47-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0183"},{"key":"bibr49-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01310.x"},{"key":"bibr50-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.32.15_suppl.10071"},{"key":"bibr52-1535370217706952","doi-asserted-by":"publisher","DOI":"10.1188\/09.CJON.157-159"}],"container-title":["Experimental Biology and Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1535370217706952","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1535370217706952","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1535370217706952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:49:18Z","timestamp":1777571358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ebm-journal.org\/journals\/experimental-biology-and-medicine\/articles\/10.1177\/1535370217706952\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,21]]},"references-count":48,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1177\/1535370217706952"],"URL":"https:\/\/doi.org\/10.1177\/1535370217706952","relation":{},"ISSN":["1535-3702","1535-3699"],"issn-type":[{"value":"1535-3702","type":"print"},{"value":"1535-3699","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,21]]}}}