Differential methylation and expression of genes in thehypoxia-inducible factor 1 signaling pathway are associated withpaclitaxel-induced peripheral neuropathy in breast cancer survivors and withpreclinical models of chemotherapy-induced neuropathic pain

摘要

Paclitaxel is an important chemotherapeutic agent for the treatment of breastcancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a majordose-limiting toxicity that can persist into survivorship. While not allsurvivors develop PIPN, for those who do, it has a substantial negativeimpact on their functional status and quality of life. No interventions areavailable to treat PIPN. In our previous studies, we identified that theHIF-1 signaling pathway (H1SP) was perturbed between breast cancer survivorswith and without PIPN. Preclinical studies suggest that the H1SP is involvedin the development of bortezomib-induced and diabetic peripheral neuropathy,and sciatic nerve injury. The purpose of this study was to identify H1SPgenes that have both differential methylation and differential geneexpression between breast cancer survivors with and without PIPN.