Graduate School of Frontier Sciences, The University of Tokyo Department of
Integrated Biosciences

In Japan, one out of every two people suffers from cancer. Nearly one million people are newly diagnosed with cancer every year, and this number is expected to continue to increase. In addition to the progress of new technologies such as comprehensive genome analysis, the development of molecular targeted drugs and immunotherapy based on the understanding of the biological characteristics of cancer has steadily improved the therapeutic outcome of cancer, but new issues such as cancers for which no effective therapeutic target can be found and resistance to therapeutic drugs have become apparent. To create the optimal treatment for each individual patient, a deep biological understanding of not only the cancer cells but also the surrounding microenvironment is required. To make this possible, it is essential to analyze patient samples undergoing treatment, add insights based on the clinical information, and share the results with internal and external researchers both in the academia and industry. Faculty members in the Laboratory of Cancer Biology belong to the Exploratory Oncology Research and Clinical Trial Center (EPOC) of the National Cancer Center and are engaged in translational research in collaboration with the National Cancer Center Hospital East, which is conducting top-class clinical development in Japan. Let's create the next generation of Precision Oncology together.

Cancer is a complex tissue composed of cancer cells and their surrounding non-cancerous cells. Therefore, to reproduce the human tumor microenvironment, it is necessary to establish an assay system that includes not only cancer cells but also non-cancer cells. In this field, we are focusing on fibroblasts (CAFs), which are representative of non-cancer cells. Recent studies have shown that CAFs are a functionally and morphologically heterogeneous population of cells. We have isolated and cultured CAFs from many cancer specimens and constructed a microenvironment formed by these CAFs and cancer cells using fluorescent proteins, time lapse imaging, and organoid production techniques to elucidate the mechanism of cancer development and drug sensitivity.

Drug delivery system (DDS) is a method of tumor-selective delivery of anticancer drugs to enhance their efficacy and minimize their side effects. We are conducting unique drug discovery research of next-generation antibody drugs such as ADC (antibody-drug conjugate), RIT (radioimmunotherapy), and BsAb (bispecific antibody) with using series of technologies such as molecular imaging to visualize their delivery, mass spectrometry, bioinformatics, and molecular and cell biology methods to enhance host immune response to attack cancer cells. In addition, we are developing new diagnostic and therapeutic methods which target cancer smell and biomolecules.

Deeply understanding “cancer hallmarks and vulnerability” is important to develop novel cancer therapeutic drugs. Chromosomal instability (CIN), which is one of the major cancer hallmarks, provokes various oncogenic cellular stresses to generate CIN-mediated cancer vulnerabilities. Targeting the CIN-mediated cancer vulnerabilities, we are committed to discover the innovative cancer therapeutics candidates in collaboration with numbers of academia, biotech companies, and pharmaceuticals.

High quality clinical information is necessary for the development of cancer therapies. In addition, data from multi-omics analysis of genome, transcriptome, and microbiome using patient samples and animal and cell models is also essential. Informatics is essential for integrating these data and deriving new knowledge. We are engaged in research and development of various data processing pipelines, database construction, optimization techniques for efficient extraction of relevant information, and visualization.

While mRNA vaccines have been a great success in developing COVID-19 vaccines, no cancer vaccines have been approved, and there is currently a global race to develop　one.　Clinical development of CAR/TCR-T cells is lagging far behind the United States, China, and Europe. Still, no one has demonstrated efficacy in solid tumors; this is also a global competition. This method has many problems, including its high cost, complexity, and safety concerns, and there are few clinical trials in Japan, so it has not become widespread. Our laboratory has selected 10 common cancer antigens that cover a wide range of solid cancers. We aim to develop a cancer mRNA vaccine that combines these molecules and develop a low-cost, simple, and safe T cell therapy that involves transiently expressing and administering multiple CARs or TCRs that target these molecules in T cells. Our goal is to provide recurrence prevention and treatment to all cancer patients.

Cancer progresses through highly intricate rules across multiple levels, including tissue architecture, cellular biology, and molecular pathways, from its initiation to progression and therapeutic modulation. Decoding the“code”of cancer demands profound insights into histopathology, combined with cutting-edge, innovative technologies for precise analysis.

In our laboratory, we employ advanced approaches such as spatial genomics, single-cell RNA sequencing, and functional genomics screening using shRNA and CRISPR libraries to gather and analyze vast amounts of data. Through this data-driven strategy, we are not only striving to unravel the molecular mechanisms of cancer but are also pushing the boundaries to identify groundbreaking therapeutic targets and discover novel drug seeds that have yet to be explored.