Role of microRNAs in fluoropyrimidine-related toxicity: what we know

Area of Science:

• Oncology
• Pharmacogenomics
• Molecular Biology

Background:

• Fluoropyrimidines are widely used cancer chemotherapeutics, treating millions annually.
• Fluoropyrimidine chemotherapy causes severe toxicity in 30-40% of patients, sometimes leading to fatal outcomes.
• Dihydropyrimidine dehydrogenase (DPD) activity is critical in fluoropyrimidine metabolism and toxicity; DPD deficiency increases adverse event risk.

Purpose of the Study:

• To review the current understanding of microRNA (miRNA) involvement in fluoropyrimidine toxicity.
• To highlight miR-27 as a predictive factor for fluoropyrimidine-induced adverse events.
• To identify new research avenues concerning miRNAs and fluoropyrimidine toxicity.

Main Methods:

• Literature review of studies on fluoropyrimidine toxicity.
• Analysis of genetic factors, including DPYD variants and miRNA expression.
• Synthesis of existing data on miRNA mechanisms in drug-induced toxicity.

Main Results:

• DPD deficiency, identified through DPYD genotyping, is a known risk factor for fluoropyrimidine toxicity.
• Overexpression of miR-27 is identified as a significant predictive factor for fluoropyrimidine toxicity.
• miRNAs play a crucial role in modulating the metabolic pathways and cellular responses to fluoropyrimidines.

Conclusions:

• miRNAs, particularly miR-27, represent a promising area for predicting and potentially mitigating fluoropyrimidine toxicity.
• Further research into miRNA-based biomarkers and therapeutic strategies could improve cancer patient outcomes.
• Integrating genetic and miRNA profiling may offer a more comprehensive approach to personalized fluoropyrimidine chemotherapy.