Metabolic enzyme-based cancer therapy: Mechanisms, delivery strategies, and translational challenges.

Cancer remains one of the leading causes of global mortality, underscoring the need for therapeutic strategies that are both effective and selective. Enzyme-based cancer therapy has emerged as a promising approach by exploiting tumor-specific metabolic dependencies, redox vulnerabilities, and nutrient auxotrophy. This review critically examines recent advances in anticancer enzyme therapy, focusing on amino acid-degrading and redox-modulating enzymes, their mechanisms of action, and translational potential. We integrate insights across enzyme classes to highlight shared therapeutic principles, common limitations, and emerging resistance mechanisms. In addition, we discuss advanced delivery and engineering strategies-including PEGylation, encapsulation, fusion proteins, and genetic manipulation-designed to enhance stability, targeting, and clinical efficacy. Particular emphasis is placed on rational combination strategies, especially the integration of enzyme therapy with autophagy modulation. Collectively, this review provides a conceptual framework for the future development of enzyme-based cancer therapeutics.