Current opinion on the pharmacogenomics of paclitaxel-induced toxicity

Abstract

Introduction: Paclitaxel is a microtubule stabilizer that is currently one of the most utilized chemotherapeutic agents. Its efficacy in breast, uterine, lung and other neoplasms made its safety profile enhancement a subject of great interest. Neurotoxicity is the most common paclitaxel-associated toxicities. In addition, hypersensitivity reactions, hematological, gastrointestinal, and cardiac toxicities are all encountered. Areas covered: The current review explores paclitaxel-induced toxicities mechanisms and risk factors. Studies investigating these toxicities pharmacogenomic biomarkers are reviewed and summarized. There is a limited margin of consistency between the retrieved associations. Variants in genes related to neuro-sensitivity are the most promising candidates for future studies. Expert opinion: Genome-wide association studies highlighted multiple-candidate biomarkers relevant to neuro-sensitivity. Most of the identified paclitaxel-neurotoxicity candidate genes are derived from congenital neuropathy and diabetic-induced neurotoxicity pathways. Future studies should explore these sets of genes while considering the multifactorial nature of paclitaxel-induced neurotoxicity. In the absence of certain paclitaxel-toxicity biomarkers, future research should avoid earlier studies’ caveats. Genes in paclitaxel’s pharmacokinetic pathways could not provide consistent results in any of its associated toxicities. There is a need to dig deeper into toxicity-development mechanisms and personal vulnerability factors, rather than targeting only the genes suspected to affect drug exposure.

Keywords: Paclitaxel-Induced Toxicities, Chemotherapy-Induced Neurotoxicity, Pharmacogenomics Biomarkers, Genome-Wide Association Study (GWAS), Targeted-Gene Studies, Cancer