Enzymatic Applications in Cancer Therapy

Enzymatic approaches to cancer therapy harness the catalytic power of proteins to interfere selectively with tumour metabolism, to activate prodrugs at the tumour site or to modulate the tumour microenvironment. The archetypal example is l-asparaginase, which depletes extracellular l-asparagine and induces apoptosis in asparagine-auxotrophic leukaemia cells. Beyond this, novel enzyme-prodrug systems exploit tumour-associated proteases or engineered enzymes to convert non-toxic prodrugs into cytotoxic agents selectively within the tumour milieu. Enzyme engineering has broadened the applicability of these systems by improving substrate specificity, reducing immunogenicity and extending systemic half-life through strategies such as PEGylation and protein backbone modification. Nanocarrier-based delivery and antibody–enzyme conjugates enable localisation of catalytic activity to the tumour, minimising damage to healthy tissues. Advances in structural biology and biophysical methods have deepened understanding of enzyme dynamics and allostery, guiding the rational design of next-generation biocatalysts. Concurrently, innovative purification and immobilisation platforms, including supported ionic liquid materials, are reducing production costs and facilitating scale-up. Together, these developments underscore a multifaceted landscape in which enzyme-driven modalities offer precision, reduced systemic toxicity and the capacity to address drug-resistant and hard-to-treat malignancies.

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Enzymatic Applications in Cancer Therapy publication trend

The graph below shows the total number of articles in enzymatic applications in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

L-Asparaginase: An enzyme that hydrolyses l-asparagine to l-aspartate and ammonia, depriving certain tumour cells of an essential amino acid and triggering apoptosis.

Michaelis–Menten constant (Km): A measure of the substrate concentration at which an enzyme operates at half its maximum velocity, reflecting enzyme-substrate affinity.

Heteronuclear single-quantum correlation (HSQC) NMR: A two-dimensional NMR technique that correlates proton and heteronucleus (e.g. carbon) chemical shifts, enabling insight into protein structure and dynamics.

PEGylation: The covalent attachment of polyethylene glycol chains to proteins to enhance solubility, reduce immunogenicity and prolong circulation time.

Supported ionic liquid phase (SILP): A material combining ionic liquid functionality with a solid support for selective capture or purification of biomolecules in flow-through processes.

References

1. Profiling Enzyme Activity of l‑Asparaginase II by NMR-Based Methyl Fingerprinting at Natural Abundance. Journal of the American Chemical Society (2023).
2. A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models. Cancer Letters (2024).
3. A flow-through strategy using supported ionic liquids for L-asparaginase purification. Separation and Purification Technology (2023).