Identification of pharmacogenetic target genes associated with chemotherapy-induced peripheral neuropathy.

e13541 Background: Chemotherapy-induced Peripheral Neuropathy (CIPN) is a dose-limiting toxicity of many anticancer drugs, including taxanes, vinca alkaloids and platinating agents. There are no effective means to predict which patients are at risk for CIPN nor are there effective treatments. Therefore, we have used a whole genome approach in lymphoblastoid cell lines (LCLs) alone or combined with clinical study data to identify target genes associated with CIPN that we tested further in Neuroscreen-1 (NS-1: rat pheochromocytoma) cells and human neurons derived from induced pluripotent stem cells (iCell neurons). Methods: For selecting candidate target genes, we compared published genome-wide association studies (GWAS) results of sensory peripheral neuropathy in cancer patients receiving paclitaxel with GWAS results of pharmacologic phenotypes in LCLs after paclitaxel treatment. We evaluated neurotoxic drug-induced cell growth inhibition using Cell Titer Glo and neurite parameters of outgrowth, processes ...