Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2017; 23(42): 7551-7562
Published online Nov 14, 2017. doi: 10.3748/wjg.v23.i42.7551
Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/mTOR inhibitor
Winn Aung, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Yoshinori Ukai, Katsushi Kouda, Yoshikazu Kurosawa, Takako Furukawa, Tsuneo Saga, Tatsuya Higashi
Winn Aung, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Tatsuya Higashi, Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Chiba 263-8555, Japan
Yoshinori Ukai, Katsushi Kouda, Perseus Proteomics Inc., Tokyo 153-0041, Japan
Yoshikazu Kurosawa, Innovation Center for Advanced Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan
Takako Furukawa, Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya 461-8673, Japan
Tsuneo Saga, Department of Diagnostic Radiology, Kyoto University Hospital, Kyoto 606-8507, Japan
Author contributions: Aung W designed the research, performed the majority of experiments, analyzed the data and wrote the manuscript; Ukai K, Kouda K and Kurozawa Y provided the anti-integrin α6β4 antibody; Sudo H perfomed the antibody radiolabeling; Sugyo A participated in the animal experiments; Tsuji AB, Higashi T, Furukawa T and Tsuneo S coordinated the research and helped for the manuscript preparation; all authors revised and endorsed the final draft.
Supported by (partially) a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, No. 17K10460 to Aung W.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of National Institute of Radiological Sciences.
Conflict-of-interest statement: The authors declare no potential conflicts of interest relevant to this article.
Data sharing statement: All relevant data were presented in the manuscript. Further information is available from the corresponding author at
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Winn Aung, MBBS, PhD, Senior Researcher, Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Telephone: +81-43-3823706 Fax: +81-43-2060818
Received: June 23, 2017
Peer-review started: June 26, 2017
First decision: July 13, 2017
Revised: July 31, 2017
Accepted: September 9, 2017
Article in press: September 9, 2017
Published online: November 14, 2017
Core Tip

Core tip: We examined whether the therapeutic effect of 90Y-labeled anti-α6β4 integrin antibody (ITGA6B4)-mediated radioimmunotherapy (RIT) is improved by dual PI3K/mTOR inhibitor BEZ235 in the treatment of pancreatic cancer xenograft. There is no report about the combined therapeutic effects of RIT and BEZ235 in cancer treatment, though BEZ235 has been tested for its anticancer and potential radiosensitizing effect. Our studies (in vitro/in vivo) and results suggest for the first time that it is possible to improve the therapeutic efficacy by combining 90Y-ITGA6B4-RIT and BEZ235 and this combination can be a potential encouraging treatment modality in the future.