Genetic interactions, synthetic lethality and complexity in cancer vulnerability mapping—Insights and perspectives from the 2nd EuroDepMap symposium

Large-scale perturbational approaches have transformed cancer research, enabling systematic identification of tumour-specific dependencies and therapeutic vulnerabilities. However, many clinically relevant vulnerabilities arise from genetic interactions, including synthetic lethal and buffering relationships, and are shaped by cellular state, lineage and treatment history. Interpreting complex dependency landscapes increasingly relies on advanced computational and AI-based approaches integrating molecular, phenotypic and contextual information. In this rapidly evolving setting, dedicated forums are needed to connect experimental and computational perspectives. Following the success of the inaugural European Cancer Dependency Map Symposium, the 2nd EuroDepMap was held on 20 November 2025 at Human Technopole in Milan, bringing together leading scientists in functional genomics, genome-editing screens, disease models and AI-driven analysis, marking a pivotal moment for the field.