Drug Metabolism in Personalized Oncology: From Molecular Mechanisms to Clinical Translation
A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".
Deadline for manuscript submissions: 30 October 2026 | Viewed by 3
Special Issue Editor
Special Issue Information
Dear Colleagues,
The revolution in targeted cancer therapy has fundamentally altered the therapeutic landscape, moving clinicians away from the indiscriminate toxicity of traditional chemotherapy toward precision-guided interventions. Yet, despite sophisticated drug design and increasingly refined understanding of oncogenic mechanisms, a critical challenge persists: the extraordinary interindividual variability in drug response, efficacy, and adverse reactions among patients receiving identical treatments.
This variability is not a mystery of pharmacodynamics but rather a consequence of pharmacokinetics—specifically, how individual patients absorb, distribute, metabolize, and eliminate drug molecules. While drug design efforts focus intensely on molecular target selectivity, the clinical performance of these drugs is equally shaped by the body's biochemical machinery for processing xenobiotics. Drug-metabolizing enzymes are remarkably diverse in their structure, catalytic mechanisms, tissue distribution, and regulation. Genetic polymorphisms in these enzymes create substantial interindividual differences: a poor metabolizer may accumulate toxic drug concentrations despite standard dosing, while an ultra-rapid metabolizer may achieve subtherapeutic exposure and treatment failure.
For anticancer drugs, where therapeutic windows are often narrow and adverse events can be severe, this variability carries profound clinical consequences. A patient's genetically determined capacity to metabolize a tyrosine kinase inhibitor, chemotherapy agent, or immunotherapy adjuvant directly influences both the likelihood of therapeutic response and the risk of dose-limiting toxicity. Despite this critical importance, drug metabolism remains largely peripheral to clinical cancer care, and pharmacogenomic guidance for drug-metabolizing enzyme variants is rarely implemented in practice.
This Special Issue of Molecules is dedicated to repositioning drug metabolism at the center of precision oncology. We invite research spanning the full breadth of how cancer drugs are biotransformed: biochemical characterization of enzymatic transformations using kinetic methods and analytical chemistry; computational studies employing molecular docking and molecular dynamics simulations to predict drug-enzyme interactions and the functional consequences of genetic variants; investigations of how polymorphisms in metabolizing enzymes alter drug exposure and clinical outcomes.
Dr. Gianluca Catucci
Guest Editor
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Keywords
- drug metabolism
- anticancer drugs
- polymorphisms
- enzymes
- drug biotransformation
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