Related Experiment Video
Updated: Aug 5, 2026
Microfluidics-based High-throughput Circulating Tumor Cell Sorting and Single-cell Sequencing Technology
Published on: November 14, 2025
AI-integrated multi-omics platform to revolutionize anti-metastatic therapy development through circulating tumor
Tadayoshi Hashimoto1,2,3, Taro Shibuki1,4, Takao Fujisawa1,5
1Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
Background:
Metastatic disease remains the leading cause of cancer-related death, yet most precision oncology strategies still emphasize profiling primary tumors and tracking cell-free tumor DNA (ctDNA). Although ctDNA has transformed genomic profiling, molecular residual disease monitoring, and early cancer detection, it cannot directly capture viable tumor cell states, phenotypic plasticity, or functional adaptations that drive metastatic spread. We propose that the next phase of precision oncology should integrate the cellular dimension of metastasis through systematic circulating tumor cell (CTC) profiling.
Methods:
The SCRUM-MONSTAR platform, one of the largest pan-cancer molecular profiling initiatives in Japan, offers an exceptional foundation for this transition through its nationwide infrastructure for multi-omics analysis, longitudinal biospecimen collection, and artificial intelligence-enabled clinical interpretation. By combining matched tissue profiling, serial ctDNA analysis, single-cell CTC transcriptomics, metabolomics, and organoid- and mouse-based functional modeling, SCRUM-MONSTAR-CTC could evolve into a translational ecosystem for anti-metastatic drug discovery. Within this framework, we highlight adherent-to-suspension transition (AST) as one representative, experimentally tractable plasticity program that enables tumor cells to survive in circulation and subsequently colonize distant organs.
Discussion:
We envision that identifying and therapeutically targeting AST-related and other metastatic plasticity programs across tumor types will provide a path toward clinically actionable anti-metastatic therapies. More broadly, this framework could enable the identification of metastatic vulnerabilities, the development of biomarker-guided anti-metastatic trials, and the reverse translation of patient-derived discoveries into early-phase clinical testing. Precision oncology must move beyond cataloging tumor genomes and begin targeting metastasis as a dynamic biological process.
Trial Registration:
UMIN000056873, approved by the Institutional Review Board of the National Cancer Center Hospital East.
Insights
Precision oncology needs to integrate circulating tumor cell (CTC) profiling to target metastasis. This approach, using the SCRUM-MONSTAR platform, focuses on cellular plasticity to develop new anti-metastatic therapies.
Area of Science:
- Oncology
- Cancer Metastasis Research
- Translational Medicine
Background:
- Metastatic disease is the primary cause of cancer mortality, with current precision oncology focusing on primary tumors and cell-free tumor DNA (ctDNA).
- ctDNA analysis, while valuable, cannot capture the dynamic cellular states and adaptations driving metastasis.
- Integrating circulating tumor cell (CTC) profiling is proposed as the next frontier in precision oncology.
Purpose of the Study:
- To propose a framework for integrating CTC profiling into precision oncology to combat metastasis.
- To leverage the SCRUM-MONSTAR platform for multi-omics analysis of CTCs.
- To identify and target cellular plasticity programs that drive metastatic spread.
Main Methods:
- Utilizing the SCRUM-MONSTAR platform for nationwide multi-omics analysis and longitudinal biospecimen collection.
- Combining matched tissue profiling, serial ctDNA analysis, and single-cell CTC transcriptomics.
- Employing metabolomics and functional modeling (organoid and mouse) to study metastatic processes like adherent-to-suspension transition (AST).
Main Results:
- The SCRUM-MONSTAR-CTC framework facilitates a translational ecosystem for anti-metastatic drug discovery.
- Adherent-to-suspension transition (AST) is identified as a key plasticity program enabling tumor cell survival in circulation and distant organ colonization.
- The study highlights the potential for identifying metastatic vulnerabilities and developing targeted therapies.
Conclusions:
- Targeting AST and other metastatic plasticity programs offers a pathway to clinically actionable anti-metastatic therapies.
- This framework can guide the development of biomarker-guided anti-metastatic trials and accelerate reverse translation.
- Precision oncology must evolve to target metastasis as a dynamic process, beyond genomic profiling.
