1-CS-3
LAT1を標的とした新規抗がん剤の医師主導治験
Investigator-initiated clinical trial of an anti-cancer drug targeted on LAT1
〇疋田 隼人1、原田 秀明2、重川 稔1、加藤 将夫3、永森 收志4、金井 好克5、竹原 徹郎1
Hayato Hikita1, Hideaki Harada2, Minoru Sigekawa1, Yukio Kato3, Shushi Nagamori4, Yoshikatsu Kanai5, Tetsuo Takehara1
1大阪大学大学院医学系研究科消化器内科学、2大阪大学医学部附属病院、3金沢大、4奈良県立医科大、5大阪大・院医
1Dept. Gastroenterology and Hepatology, Grad. Sch. Med., Osaka Univ., 2Dept. Medical Innovation, Osaka University Hospital, 3Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa Univ., 4Dept. Collaborative Research for Bio-Molecular Dynamics, Nara Medical Univ., 5Dep. Bio-system Pharmacology, Grad. Sch. Med., Osaka Univ.
LAT1 (L-type amino acid transporter 1: SLC7A5) is an amino acid transporter. While normal cells intake amino acids by LAT2, tumor cells intake amino acids by LAT1. In pancreatic cancer, LAT1 is overexpressed in tumor cells, and high expression of LAT1 is a predictive factor of poor prognosis. To date, LAT1 competitive-inhibitors, such as BCH and JPH203, were developed, and they are reported to be effective against various cancer cells in vitro and xenograft model. However, LAT1 non-competitive-inhibitors have not been developed.
Recently, we developed a LAT1 non-competitive-inhibitor and confirmed its anti-cancer effect against several cancer cells in vitro and xenograft model. Its oral administration also improved overall survival of genetically engineered mice with pancreatic ductal adenocarcinoma. After examining several nonclinical tests for the safety, we decided to move to the next step to acquire clinical proof of concept. To this end, we planned an investigator-initiated first in human clinical trial. After approved by institutional review board and clinical trial notification to PMDA, the trail has started and is ongoing. In the present session, we introduced our experienced process and various challenges to the investigator-initiated clinical trial.