Annual Report 2021

Division of Strategic Programs

Yoshikatsu Koga, Katsuya Tsuchihara, Yoshinori Ikarashi, Katsuji Aikawa, Shingo Sakashita, Masahiro Yasunaga, Daichi Ota

Introduction

 Translational research aimed at "Conquer and Cure Cancer" (the 3Cs) is conducted in the Exploratory Oncology Research & Clinical Trial Center (EPOC). The Department of Strategic Programs improves the quality of research by establishing appropriate quality control systems for research facilities, education systems for researchers, and appropriate quality control systems for research samples. We manage several EPOC projects, which are project-type research composed of multiple basic and clinical departments that aim to achieve clinical goals. A "Section of Liaisons for Translational Research", "Section of Seed Selection and Evaluation", "Section of Project Management", "Section of Public Relations for Translational Research", and "Section of Education and Career Development for Translational Research" have been established in the Department in order to disseminate various medical seeds to the world, through collaboration with domestic/overseas academia/companies, from EPOC and the Center for Promotion of Translational Research (CPOT) founded in July 2021. We also manage the development of medical seeds and career development of project managers. In December 2021, the National Cancer Center was accredited as a Center for Advancing Translational Research (CATR) by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and the Department of Strategic Programs fulfills the secretariat function for CPOT.

The Team and What We Do

• EPOC research projects
   “Project for Resistance to Cancer Therapies”: During the funded period, we established the SOPs for the generation, storage, and usage of clinical samples. Using these samples, we successfully conducted multiomics analyses. The results led to the identification of several novel mechanisms of resistance to cancer therapies in lung cancer. We will continue our efforts to collect samples and aim to uncover mechanisms of resistance to cancer therapies.
   “Project for Medical Device Development”: In this project, various types of cutting machines, welding machines, and 3D printers were installed in the NCC for medical device development. Technologies in the field of robotics and imaging were developed through collaboration with academia, and we obtained one NCC grant, three Grants-in-Aid for Scientific Research, and one AMED grant up to FY2021.
   “Project for Co-clinical Trials”: The milestone “Establishment of co-clinical trial systems” was achieved through the establishment of SOPs for the generation of various non-clinical models and through collaboration with clinicians. However, the milestone “Start of co-clinical trials” was not achieved at the end of the supported period. In the future, we will develop new non-clinical models such as perfusable cancer organoids as well as establishing evaluation systems for drug efficacy.
   “Project for Supportive Care Research”: The Project for Supportive Care Research has been active since 2020. In this project, we are conducting translational research from non-clinical research to first-in-human studies for the development of novel analgesics and drugs for anti-cancer drug-relevant cardiotoxicity. This year we identified a drug candidate and its target proteins for the treatment of cardiotoxicity caused by doxorubicin. Currently, we have started research to establish proof of concept (POC) in non-clinical trials.
   “Project for Prevention of HPV-related Cancer”: By using double nicking of HPV genomes with CRISPR/Cas9, we are developing a new therapy of HPV-associated cancers. We identified the best combinations of 8 gRNAs targeting the E6E7 region of HPV16 or HPV18. Five organoid strains have been established from 9 cases of oropharyngeal cancer.
   “Project for Fully Automatic Specimen Preparation”: A joint research agreement was concluded with Sakura Finetek Japan Co. Ltd. Fully automated processing equipment, a fully automated embedding machine, and a fully automated staining machine were installed in the cancer center. Sampling was performed from surgical materials for esophageal, gastric, and colorectal cancer, and preparation of HE specimens with various thicknesses and staining conditions was started.

Education

 Various lectures, such as lectures on gene recombination experiments, biohazard/chemohazard experiments, and human clinical samples, were held as education for researchers.

Future Prospects

 The Department of Strategic Programs will manage and support the research in each division of EPOC as a common department of it and a secretariat of CPOT.

List of papers published in 2021

Journal

1. Takashima K, Koga Y, Anzai T, Migita K, Yamaguchi T, Ishikawa A, Sakashita S, Yasunaga M, Yano T. Evaluation of Fluorescence Intensity and Antitumor Effect Using Real-Time Imaging in Photoimmunotherapy. Pharmaceuticals (Basel, Switzerland), 15:2022

2. Takashima H, Koga Y, Manabe S, Ohnuki K, Tsumura R, Anzai T, Iwata N, Wang Y, Yokokita T, Komori Y, Mori D, Usuda S, Haba H, Fujii H, Matsumura Y, Yasunaga M. Radioimmunotherapy with an 211 At-labeled anti-tissue factor antibody protected by sodium ascorbate. Cancer science, 112:1975-1986, 2021

3. Manabe S, Takashima H, Ohnuki K, Koga Y, Tsumura R, Iwata N, Wang Y, Yokokita T, Komori Y, Usuda S, Mori D, Haba H, Fujii H, Yasunaga M, Matsumura Y. Stabilization of an 211At-Labeled Antibody with Sodium Ascorbate. ACS omega, 6:14887-14895, 2021

4. Sekiguchi M, Kakugawa Y, Ikematsu H, Hotta K, Konda K, Tanaka Y, Takamaru H, Yamada M, Sakamoto T, Saito Y, Imai K, Ito S, Koga Y, Iwasaki M, Murakami Y, Matsuda T. Risk Stratification Score Improves Sensitivity for Advanced Colorectal Neoplasia in Colorectal Cancer Screening: The Oshima Study Workgroup. Clinical and translational gastroenterology, 12:e00319, 2021