[Biomarker exploration and its clinical use]

Area of Science:

• Pharmacogenomics
• Metabolomics
• Biomarker Discovery

Context:

• Biomarkers are crucial for predicting disease severity and drug response, yet few are clinically implemented.
• Academic research has yielded numerous potential biomarkers, but translation into clinical practice remains limited.

Purpose:

• To review advancements in genomic and metabolomic biomarker discovery for drug development and clinical application.
• To highlight key findings in pharmacogenomic analysis of irinotecan and severe adverse drug reactions (SJS/TEN).
• To explore metabolomic biomarkers for disease phenotyping and prediction, focusing on Alzheimer's disease and dilated cardiomyopathy.

Summary:

• Pharmacogenomic analysis identified UGT1A1 variants associated with irinotecan-induced neutropenia and HLA variants linked to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) from allopurinol and carbamazepine.
• Metabolomic studies in animal models revealed lipid metabolite changes in dilated cardiomyopathy and identified specific oxidized fatty acids in Alzheimer's disease models as potential predictive biomarkers.
• The review discusses critical issues for biomarker research and development, aiming to facilitate novel biomarker identification and qualification in Japan.

Impact:

• Research findings have been cited in the package inserts for irinotecan and allopurinol, demonstrating clinical relevance.
• Identified biomarkers can improve drug development efficiency and personalize medicine.
• The review aims to guide future biomarker research, particularly for early-career scientists in pharmaceutical sciences.