Abstract 1154: SCRUM-Japan MONSTAR-SCREEN-3: A large-scale multi-institutional prospective study platform integrating spatial transcriptomics and multi-omics analysis for comprehensive understanding of tumor microenvironment dynamics
Authors: Mitsuho Imai, Shingo Sakashita, Junichiro Yuda, Shin Kobayashi, Riu Yamashita, Tadayoshi Hashimoto, Takao Fujisawa, Taro Shibuki, Shun-Ichiro Kageyama, Yoshikatsu Koga, Michiko Nagamine, Takeshi Kuwata, Hideaki Bando, Yoshiaki Nakamura, Woong-Yang Park, Takayuki Yoshino
Journal: Cancer Research (2025)

Background: The SCRUM-Japan MONSTAR-SCREEN and CIRCULATE-Japan platforms have successfully implemented organ-agnostic liquid biopsy-based precision oncology and molecular residual disease (MRD)-guided therapeutic development, leading to multiple regulatory approvals of therapeutic agents and diagnostics through collection of quality-assured clinical data. Understanding tumor heterogeneity and microenvironment dynamics remains fundamental to advancing precision medicine. Here, we present MONSTAR-SCREEN-3, an innovative large-scale prospective study platform designed to integrate high-resolution spatial transcriptomics with multi-omics analysis across diverse cancer types. In our preliminary analyses, spatial transcriptomic analysis of HER2-amplified metastatic colorectal cancer revealed that treatment responses to anti-HER2 therapy are closely associated with tumor microenvironment characteristics, including increased T and B cell infiltration and interactions between cancer stem-like cells and HER2-expressing cells. Methods: MONSTAR-SCREEN-3 (UMIN000053975) is a large-scale multi-institutional study involving 55 centers across Japan, planning to enroll 3,200 patients stratified into three distinct cohorts: advanced solid tumors undergoing systemic therapy (n=1,700), resectable solid tumors receiving definitive treatment (n=1,100), and hematologic malignancies (n=400). The study implements systematic multi-sampling at strategically defined timepoints. Our comprehensive molecular characterization utilizes 5000Plex spatial transcriptomics integrated with circulating tumor DNA/RNA sequencing, bulk tissue WES/WTS, plasma proteomics, and microbiome analyses. Standardized longitudinal monitoring with WGS-based MRD analysis is implemented in resectable cases, while disease-specific MRD assessment approaches are applied to hematologic malignancies. Following SCRUM-Japan's established quality assurance system, standardized monitoring collects regulatory-grade clinical data, including objective response rate, progression-free survival, and overall survival. All molecular and clinical data will be integrated into our VAPOR CONE supercomputing infrastructure, creating an AI-driven ecosystem. This large-scale implementation of spatial transcriptomics analysis across multiple cancer types represents an unprecedented opportunity to comprehensively map the tumor microenvironment architecture and its dynamics during treatment. The integration of this spatial information with molecular and clinical data will provide unprecedented insights into tumor-immune interactions and resistance mechanisms, establishing an evidence-based framework for next-generation precision oncology. Citation Format: Mitsuho Imai, Shingo Sakashita, Junichiro Yuda, Shin Kobayashi, Riu Yamashita, Tadayoshi Hashimoto, Takao Fujisawa, Taro Shibuki, Shun-Ichiro Kageyama, Yoshikatsu Koga, Michiko Nagamine, Takeshi Kuwata, Hideaki Bando, Yoshiaki Nakamura, Woong-Yang Park, Takayuki Yoshino. SCRUM-Japan MONSTAR-SCREEN-3: A large-scale multi-institutional prospective study platform integrating spatial transcriptomics and multi-omics analysis for comprehensive understanding of tumor microenvironment dynamics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1154.