Progress Report

Challenge toward the Control of Intractable Cancer through Understanding of Molecular, Cellular, and Interorgan Networks[1] Development of technologies for collecting patient biospecimens and data for the realization of optimal medicine (My Medicine)

Progress until FY2023

1. Outline of the project

Since many intractable cancers are found as advanced cancers, clinical data and biological data derived from patients are limited, which is a major obstacle to elucidating the onset factors. In addition, the technology for acquiring various biological data from minute amounts of specimens and the mechanism for accumulating and sharing data are immature.

In this theme, we are collecting clinical specimens (blood and cancer tissue, nearby normal tissue), clinical data (blood biochemical data, images, etc.), blood, body fluids, feces, etc.

検査を受けている人のイラスト

In parallel, we are establishing and accumulating organoids from the patient tissue samples. Patient organoids can be used for various experiments that are not possible with patient samples only. They are an innovative technology that opens up great possibilities for understanding developmental processes of cancer.

手術のイラスト

We are building a database by acquiring various biological data, including genomes, from the patient tissue samples.

2. Outcome so far

Building a patient biospecimen bank:

We have obtained approval from the ethics committee for common efforts at Keio University, Kyoto University, and Kobe University. Surplus residual specimens obtained by various methods (endoscopy, surgery, etc.) are accumulated at each facility. Furthermore, we have been establishing organoids and their omics are underway.

Figure
 
Figure
Fujii et al., Nat Rev Cancer 2024.
Construction of the organoid culture platform:

We have confirmed that patient-derived organoids can be established using a standardized method, and have accumulated the number of specimens. Through comprehensive analysis, we discovered evolutionary histories of breast cancer and novel molecular mechanisms by which progress pancreatic cancer.

Nishimura et al., Nature 2023.
Nishimura et al., Nature 2023.
Masuda et al., J Clin Invest 2023.
Masuda et al., J Clin Invest 2023.

Furthermore, we have developed new organoid culture techniques including vascular organoid s and co-culture with fibroblasts.

Kawakami et al., Cell Stem Cell 2023.
Kawakami et al., Cell Stem Cell 2023.
Construction of a multi-level integrated analysis shared database:

We have advanced the development of a whole-genome data analysis infrastructure for clinical specimens and organoids. RNA analysis has also progressed. Furthermore, we have been acquiring comprehensive lipid metabolite profiles, lipid mediator profiles and exosome profiles. The standardization of protocols for metabolic analysis are progressing.

 
Nishimori et al., Sci Rep 2024.
Nishimori et al., Sci Rep 2024.

3. Future plans

Samples of precancerous lesions, very early cancers, and advanced cancers have been collected, and patient organoids have been established. Along with the progress, we will proceed with the analysis using the platform of multi-level integrated analysis.