Current opinion on the pharmacogenomics of paclitaxel-induced toxicity

Area of Science:

• Oncology
• Pharmacogenomics
• Toxicology

Background:

• Paclitaxel is a widely used chemotherapeutic agent, but its use is limited by toxicities, particularly neurotoxicity.
• Enhancing the safety profile of paclitaxel is crucial for effective cancer treatment.
• Understanding paclitaxel-induced toxicities is essential for patient management.

Purpose of the Study:

• To review mechanisms and risk factors of paclitaxel-induced toxicities.
• To summarize studies on pharmacogenomic biomarkers for paclitaxel toxicities.
• To identify promising biomarkers for predicting and mitigating paclitaxel-associated adverse events.

Main Methods:

• Literature review of studies on paclitaxel toxicities and their mechanisms.
• Systematic summary of research investigating pharmacogenomic biomarkers.
• Analysis of associations between genetic variants and paclitaxel-induced adverse events.

Main Results:

• Neurotoxicity is the most frequent paclitaxel-associated toxicity, alongside other adverse effects like hypersensitivity, gastrointestinal, and cardiac issues.
• Limited consistency was found between identified pharmacogenomic biomarkers and paclitaxel toxicities.
• Gene variants associated with neuro-sensitivity, particularly those implicated in congenital or diabetic neuropathy, show promise.

Conclusions:

• Genome-wide association studies suggest candidate biomarkers for paclitaxel-induced neurotoxicity.
• Future research should investigate neuro-sensitivity genes, acknowledging the multifactorial nature of toxicity.
• Focusing on toxicity mechanisms and individual vulnerability factors is more promising than solely targeting pharmacokinetic genes.