Progress Report

Challenge toward the Control of Intractable Cancer through Understanding of Molecular, Cellular, and Interorgan Networks[2] Technology development for integrated analysis and verification of patient biometric data

Progress until FY2024

1. Outline of the project

By utilizing the patient biospecimen bank, in addition to parent-derived genomic data, various data such as gene mutation and gene expression at the lesion site can be obtained. However, the utilization technology is currently very underdeveloped. In this theme, we will develop an integrated analysis method to reveal the key molecules and networks (molecules and cell/tissue/organ networks) in the onset process from "multi-layered data" derived from patients.

Figure

Since the amount of patient samples is very small, there is a big limitation as an experimental material. In order to overcome this, we will further evolve animal models and patient organoid models. By using patient organoids, it is possible for the first time to analyze biological responses to drugs and gene mutations. It also has great potential as an optimal drug selection system for individuals.
In addition to acquiring sequential data over time, imaging technology has the potential to lead to non-invasive diagnosis in the future. In this theme, we will proceed with the development of imaging technology (sensors and probes).

Figure

2. Outcome so far

Construction of an integrated analysis platform for "multi-layered data"

Using mouse omics data, we have developed a technique for estimating multi-hierarchical networks. We have also investigated pseudo-time analysis that arranges patient organoids at various stages along the path of onset. We have developed an exploratory image analysis technique using deep learning to predict the prognosis of pancreatic cancer from peritoneal washing cytology images. Furthermore, we have established a method for analyzing genomic abnormalities in Japanese cancers across cancer types.

Experimental Medicine Jan, 2024 (Yodosya)  Newton Mar 2025 (Newton Press)
Ito et al., Sci Rep 2023.
Ito et al., Sci Rep 2023.
Noguchi et al., Sci Rep 2024.
Noguchi et al., Sci Rep 2024.
Horie et al., Cancer Discov 2024.
Horie et al., Cancer Discov 2024.
Development of next-generation organoid system

We proceeded with the establishing of new mouse models with pancreatic cancer. We have also developed a next-generation organoid culture method using iPS cells and elucidated the prediction of progression risk due to single nucleotide polymorphisms in glucose metabolism genes. Furthermore, we have succeeded in generating liver organoids with functional multi-layered structures. This will be a new foundation for disease research, drug evaluation, and regenerative medicine.

Kimura et al., Cell 2022.
Kimura et al., Cell 2022.
Building an imaging analysis platform

We have built an imaging analysis platform that researchers can use collaboratively.健都イメージングサポート拠点

Retrospective analysis of CT images revealed that focal pancreatic atrophy can be observed several years before the onset of pancreatic cancer.

Gonda et al., United Euro Gastroenterol J 2024.
Gonda et al., United Euro Gastroenterol J 2024.

Using a modular design platform, we have developed a fluorescent probe for proteolytic enzymes, which makes it possible to detect enzyme activity in cancer tissues by fluorescence. This is expected to be applied to new diagnostic drugs to find cancer sites during surgery.

Kuriki et al., J Am Chem Soc 2023.
Kuriki et al., J Am Chem Soc 2023.
Minoda et al., J Am Chem Soc 2025.
Minoda et al., J Am Chem Soc 2025.
Tsukamoto et al., Cancer Sci 2024.
Tsukamoto et al., Cancer Sci 2024.

Live imaging analysis of pancreatic cancer patient organoids expressing biosensors revealed heterogeneous dynamics of ERK and AMPK activity.

3. Future plans

Utilizing the established organoids from very early and advanced cancer and mouse models, we will proceed with the development of integrated analysis technology for "multi-layered data." We will promote the development of next-generation organoid technology specialized for cancer research. We will continue our efforts to advance imaging technology. We will also start probe screening using clinical samples.