Transcriptomic analysis of plasma exosomes provides molecular information of response to cabazitaxel treatment in men with metastatic castration-resistant prostate cancer.

Abstract

Prostate cancer is the second most common cancer type and the second most common cancer-related cause of death in men. Cabazitaxel, a next-generation taxane, shows favorable toxicity profile and is effective in docetaxel-resistant tumors. Despite initial responses, in most cases, prostate cancer patients acquire resistance to cabazitaxel. There is a need to identify molecular markers that can monitor and predict treatment response. We performed transcriptional exosome profiling (Human Transcriptome Array-HTA 2.0) from the plasma of 19 patients with castration-resistant prostate cancer at baseline and in patients after one cycle of cabazitaxel (C1). The patients were stratified in two groups (responders and nonresponders) according to their clinical response to cabazitaxel. Gene set enrichment analysis and ingenuity pathway analysis platforms were used for gene and pathway analysis. We detected molecular differences in the exosomes from two groups of patients (nonresponders vs. responders) at baseline in pathways related to prostate cancer, oncogenic signaling, cytoskeleton, and immune system. In nonresponders, we found enrichment of cytoskeleton related gene (Stathmin-1 and ITSN1) that have been associated with resistance to cabazitaxel. Monitoring of exosomal transcripts after the first cycle of treatment revealed changes in pathways associated with response to treatment. Sequential transcriptional profiling of plasma-derived exosomes reveals differential expression of genes that may reflect resistance to cabazitaxel treatment and therapy response.