Next-Generation Artificial Intelligence Strategies for Mechanistic Cancer Target Discovery and Drug Development: A State-of-the-Art Review

Artificial intelligence (AI) is increasingly used in cancer research, enabling integrative analysis of complex biomedical data to identify actionable therapeutic vulnerabilities. This review specifically examines how AI advances mechanistic cancer target discovery and translational drug development, focusing on: (1) the processing of large-scale genomics, transcriptomics, proteomics, metabolomics, single-cell profiling, spatial, and clinical datasets using machine learning (ML) and deep learning (DL) algorithms; (2) the identification of candidate biomarkers, driver genes, dysregulated pathways, tumor dependencies, and molecular targets that traditional methods often miss; (3) the integration of multi-omics data, network biology, causal inference, and systems-level modeling to refine mechanistic understanding of cancer progression and separate functional driver events from passengers; and (4) applications in drug development, including virtual screening, molecular modeling, structure-informed target validation, drug repurposing, synthetic lethality prediction, and de novo drug design, which collectively may enhance early-stage drug discovery efficiency. The review underscores that AI serves as both a predictive tool and a platform for linking molecular mechanisms to hypothesis generation, target prioritization, and rational treatment design. Challenges such as data heterogeneity, algorithmic bias, interpretability, reproducibility, regulatory requirements, and patient privacy must be addressed for robust translation and clinical use. Future directions may focus on hybrid approaches that integrate causal modeling, explainable AI, multimodal data, and experimental validation to yield mechanistically grounded, clinically actionable insights. AI-driven approaches ultimately aim to accelerate mechanism-based cancer target discovery and enable more precise, biologically informed anticancer therapies.