IMPACT-CRC
| Patologia: | Cancro al colon-retto |
| Area Tematica: | Medicina Personalizzata |
| Data di Inizio Progetto: | 01/04/2026 |
| Data di Fine Progetto: | 01/04/2029 |
| Finanziamento: | € 500.000,00 |
| Partenariato | IRCCS Istituto Nazionale dei Tumori (Milano) KU Leuven (Belgio) Centro Nacional de Análisis Genómico (Spagna) Instituto de Investigación Sanitaria Acreditado Instituto de Investigación – Hospital Universitario Vall d’Hebron (Spagna) TU Dresden (Germania) Georg-Speyer-Haus (Germania) Data Investigation Company Europe (Belgio) |
IMPACT-CRC aims to establish robust, clinically actionable pharmacogenomic strategies to personalize immune checkpoint inhibitor (ICI) therapy in microsatellite stable (MSS) colorectal cancer (CRC). Leveraging a retrospective pilot cohort of approximately 56 CRC patients treated with botensilimab (Fc-enhanced anti-CTLA4) with or without balstilimab (anti-PD1), and a prospective cohort of 29 patients from the expanded UNICORN trial, the project will generate multi-omics data including genomics, transcriptomics, epigenomics, spatial omics, TCR profiling, and ctDNA analysis.
Deep TCR sequencing of PBMCs will be used to capture systemic immune dynamics, complemented by single-cell RNA-seq, placing TCR clonality analysis at the forefront of innovative approaches in this study. A key innovation is the integration of longitudinal ctDNA profiling using the ACT-Discover framework to detect karyotype heterogeneity and tumor evolution under therapy, led by VHIO, ensuring that both TCR and ctDNA tracking are central to the predictive modeling of tumor–immune co-evolution and treatment response.
Mouse organoid-derived models treated with ICI will provide mechanistic validation and cross-species anchoring, strengthening the translational relevance of the findings. AI/ML pipelines, including transformer-based models and spatial imaging integration, will be used to identify and validate biomarkers of response, resistance, and immune-related adverse events.
Ultimately, IMPACT-CRC will deliver a validated biomarker framework for patient stratification, guiding personalized ICI use in MSS CRC. The project aligns with EP PerMed goals by driving methodological innovation, fostering interdisciplinary collaboration, and enabling translation of pharmacogenomic insights into clinical practice.