Abstract 6879: Integrating omics-driven digital avatars with patient-derived experimental models to accelerate precision oncology.

Abstract Precision oncology increasingly depends on linking patient-specific molecular profiles to experimentally validated therapeutic response models. ValiRx and Inaphaea BioLabs are developing advanced patient-derived functional cancer models, while TwinEdge Bioscience is building large-scale Digital Avatar collections that mechanistically represent individual tumours across genomics, transcriptomics, proteomics, regulatory-network dynamics, and drug-response modules. By combining these complementary capabilities, we established a closed-loop translational framework for predicting, testing, and refining precision-treatment strategies, integrating (i) omics profiling of ValiRx’s patient-derived cancer models, and (ii) construction of mechanistic Digital Avatars using TwinEdge’s modelling engine. Methods: Avatars are formed by integrating gene expression patterns, pathway activity states, inferred regulatory network, and compound-response modules. We generated digital avatars by integrating matched multi-omics datasets - transcriptomic, genomic, proteomic, and phenotypic layers - into large-scale, mechanistic network models that capture cell-state dynamics. Each individual avatar was then embedded within a population of thousands, allowing systematic comparison to identify subgroups that respond to a given intervention through shared mechanistic signatures. These mechanistically aligned avatars were then analysed to uncover repurposing opportunities and novel biomarker candidates. Results: Across breast, ovarian, and colorectal cancer models, the Digital Avatars were shown to faithfully recapitulated tumour-specific regulatory features, including pathway activation, metabolic rewiring, and stress-response signatures. Avatar-based predictions revealed compound-specific vulnerabilities across multiple patient-derived models and uncovered previously uncharacterised mechanisms underlying differential responses to both targeted and broad spectrum agents. For certain models, observations pointed to the loss of regulation around VEGF-A, network rewiring around DNA/damage and some loss of c-Myc regulatory feedback. Together, these findings highlight the likelihood of a partial or full response, and allow suggestion of potential therapeutic intervention that would convert partial responders into full responders. Conclusion: The TwinEdge-ValiRx translational program demonstrates the power of integrating computational Digital Avatars with patient-derived functional models. This combined framework enhances mechanistic interpretability, improves drug response prediction, and accelerates preclinical decision making. These early results form a concrete proof-of-concept that Avatar based loop dynamics capture treatment specific regulatory rewiring and can guide downstream therapeutic evaluation. Citation Format: Bulak Arpat, Amel Bekkar, Michelle Barnard, Mark Eccleston, Ioannis Xenarios, Kevin Buyens, Michael Prosser. Integrating omics-driven digital avatars with patient-derived experimental models to accelerate precision oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6879.