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

Area of Science:

• Biochemistry
• Oncology
• Pharmacology

Background:

• Cancer is a leading cause of death globally, necessitating novel and selective therapeutic approaches.
• Enzyme-based cancer therapy leverages tumor-specific metabolic dependencies and vulnerabilities.
• Current strategies require enhancement for improved stability, targeting, and clinical effectiveness.

Purpose of the Study:

• To review recent advancements in anticancer enzyme therapy.
• To examine the mechanisms, limitations, and resistance of enzyme-based treatments.
• To discuss strategies for enhancing enzyme therapy efficacy and clinical translation.

Main Methods:

• Literature review of recent advances in anticancer enzyme therapy.
• Analysis of amino acid-degrading and redox-modulating enzymes.
• Evaluation of delivery and engineering strategies, including PEGylation, encapsulation, and fusion proteins.
• Exploration of combination strategies, particularly with autophagy modulation.

Main Results:

• Enzyme therapy shows potential by exploiting tumor-specific metabolic vulnerabilities.
• Delivery and engineering strategies can improve enzyme stability, targeting, and efficacy.
• Combination therapies, especially with autophagy modulation, offer enhanced therapeutic outcomes.
• Understanding resistance mechanisms is crucial for clinical success.

Conclusions:

• Enzyme-based cancer therapy is a rapidly evolving field with significant therapeutic potential.
• Advanced delivery and engineering techniques are key to overcoming current limitations.
• Rational combination strategies are essential for maximizing clinical efficacy.
• This review provides a framework for future development of enzyme-based cancer therapeutics.