Annual Report 2018
Preface
The National Cancer Research Center was designated as one of five hubs for the "Early / Exploratory Clinical Trial Hubs Development Project" in Japan by the Ministry of Health, Labour and Welfare in 2011. In 2012, the NCC- Exploratory Oncology Research & Clinical Trial Center (EPOC), spanning NCC's Kashiwa and Tsukiji campuses, was established with the aim to accelerate early-stage clinical developments and translational research (hereinafter, TR).
NCC-EPOC supported the TOP-GEAR trials on Tsukiji Campus and participated in the construction of the infrastructure of SCRUM-JAPAN on Kashiwa Campus with the aim to promote genomic medicine and advance the cross-sectional TR in NCC. In SCRUM-JAPAN, EPOC conducted gene analyses on over 5,000 cases and construction of the clinical information database throughout over 200 hospitals in Japan.
The accomplishment of each group in EPOC is as follows:
1. The Group for Clinical Research
The Group for Clinical Research has been operating with the goal to plan drug developments. Particularly, the objective is to effectively develop an unapproved academic drug seeds to a study drug in an investigatorinitiated trial by intervening in the process from the early stage with envisaging the possible future clinical development. (2) Another objective is to carry out investigator-initiated novel proof of concept (POC) and mode of action (MOA) trials using a private business seed based on the TR.
Monthly teleconferences have been held between Kashiwa and Tsukiji campuses to manage the progress on the development of seeds.
2. The Group for Translational Research
The Group for Translational Research is jointly operated by both campuses so that the NCC TR is effectively facilitated as a whole. The Division of Biomarker Discovery is developing novel diagnostic measures and biomarkers. Particularly, this division facilitates cooperative research with pharmaceutical companies to establish autologous cell lines of cancers characteristics to Asia and to carry out the non-clinical trials. The Division of Translational Genomics in Kashiwa Campus has been upholding a main theme, "Elucidation of the drug resistance mechanism against molecular target drugs". This group has been elucidating the mechanisms of drug resistance by taking advantage of state-of-the-art analysis technologies such as the next generation sequence analysis, single-cell analysis, mathematical model, molecular cellular biological analysis and the like. On Tsukiji Campus, the Division of Translational Genomics produced a gene analysis panel using a next-generation sequencer (NGS) and has been developing a test method to detect the genetic changes in somatic cells and germ cells. Specifically, "NCC Oncopanel System" was co-developed with Sysmex that can detect the changes (a mutation, amplification and fusion) on 114 genes on the genome DNA extracted from a tumor tissue or normal tissue by only one test. This system can also detect tumor mutation burden (TMB). This system was added to the national health insurance coverage list as Japan's first oncogenes profiling test. In the TI field, a field for this fiscal year was newly created with the aim to integrate Omics data based on patient specimens or model samples with clinical information so as to achieve the development of new cancer treatment. According to the accumulation of transcriptome data using the genome data based on the clinical sequence, and single-cell analysis, we have constructed model systems such as organoids in which the hypotheses obtained from the transcriptome data are testified to proceed with the analysis. The Division of Cancer Immunology is minutely analyzing changes in the dynamic immune status in the topical tumor site with the flow cytometry, CyTOF and scRNAseq using clinical samples including ICB in the topical tumor site before and after treatment. This group is carrying out a lot of this research with many pharmaceutical companies as the joint research or associated research with clinical trials with the aim to develop biomarkers for the prediction of the effect of cancer immunotherapy and more effective cancer immunotherapy. The 437 Division of Clinical Pharmacology and Translational Research has been addressing translational research in drug discovery through the establishment of the basis for pharmacokinetics, pharmacodynamics and pharmacogenetics analyses with the introduction of innovative technologies there.
3. The Group for Innovative Cancer Treatment
The Division of Clinical Pathology is facilitating translational research using human samples, based on the comprehension of characteristics of various tumors and what are clinically required for their treatment. Their objective is to construct an academic basis. Their objective is to elucidate the pathological condition of cancer, and to develop the novel diagnosis and treatment of cancer through attestation in a variety of experimental systems. Additionally, they commenced a study using AI to extract the pathological morphology which is characteristic to the pathological condition. The Division of Developmental Therapeutics established the world's first antibody capable of recognizing only insoluble fibrin. The antibody was shared with foreign academic facilities to conduct joint research with them. The Division of Cancer Immunotherapy facilitated bridging basic research for development of novel immunotherapies or prophylaxes and their clinical applications. In the Division of Psycho-Oncology and Supportive Care, the third-term "basic programs to promote cancer-fighting measures" were formulated. This program is more conscious of the development of palliative care of cancer and support of survivors. Each group in the Division of Innovative Cancer Treatment has been promoting research and development focusing on the exploration of seeds for drug discovery and development of novel medical treatments. On Kashiwa Campus, the Pathology / Clinical Laboratory Division in NCC East Hospital was equipped with a system for immune monitoring to allow the promotion of translational research with the immune translational research field.
4. The Group of Innovative Diagnostic and Therapeutic Devices
The Group of Innovative Diagnostic and Therapeutic Devices has been conducting molecular imaging research centered on nuclear medicine, optical imaging and MRIs with the aim to make cancer treatment minimally invasive and optimized. What is notable is that in the Nuclear Medicine Field, with the permission to use the α-ray nuclide, the study on nuclear medical treatment using an α-ray nuclide and theranostics has commenced. The Division of Radiation Oncology and Particle Therapy has been continuously addressing the establishment of the clinical effectiveness of the proton beam and its technical development by taking advantage of the physical property of the proton beam to show a high dosage centrality. The Division of Boron Neutron Capture Therapy will conduct the development of a hospital-installed BNCT accelerator and the non-clinical and clinical studies for the medical evolution of BNCT. The Division of Science and Technology for Endoscopy was awarded a cancer research grant "Promotion for the Medical Engineering Collaboration with Academic Facilities (31-A-11)" at Kashiwa Campus. They are forming the research basis which is necessary for collaboration with external academic facilities with an objective to gain the seeds. The research and development of new endoscopic diagnostic, therapeutic and training equipment in collaboration with companies and academia is also working well at Tsukiji Campus. The Division of Surgical Technology is developing an infrastructure to support surgical clinical trials and early clinical trials to develop innovative medical devices as a hub for the development of innovative medical devices in NCC East Hospital in cooperation with NEXT. Another objective is to formulate a roadmap for the development of innovative medical devices.
5. Collaboration facilities
The launch of a division which supports and manages animal experiments along with a research planning and promotion division is being considered.
Atsushi Ochiai, M.D., Ph.D.
Exploratory Oncology Research & Clinical Trial Center