Extracellular Vesicles in Advanced Prostate Cancer: Tools to Predict and Thwart Therapeutic Resistance

Abstract

Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death among men worldwide. At first, advanced PCa is treated by androgen deprivation therapy with a good initial response. Nevertheless, recurrences occur, leading to Castrate-Resistance Prostate Cancer (CRPC). During the last decade, new therapies based on inhibition of the androgen receptor pathway or taxane chemotherapies have been used to treat CRPC patients leading to an increase in overall survival, but the occurrence of resistances limits their benefits. Numerous studies have demonstrated the implication of extracellular vesicles (EVs) in different cancer cellular mechanisms. Thus, the possibility to isolate and explore EVs produced by tumor cells in plasma/sera represents an important opportunity for the deciphering of those mechanisms and the discovery of biomarkers. Herein, we summarized the role of EVs in therapeutic resistance of advanced prostate cancer and their use to find biomarkers able to predict these resistances.

Keywords: extracellular vesicles; predictive biomarkers; prostate cancer; therapeutic resistances.

Figure 1

Clinical evolution of PCa and the main challenges for research.

Figure 2

The main mechanisms of therapeutic resistance induced by EVs in prostate tumor cells. Roles of EVs have been demonstrated in the induction of tumor plasticity, elimination of drug inducing drug efflux or augmentation of gene expression or protein/mRNA transfer via EVs. EMT = Epithelial to Mesenchymal Transition, NED = Neuroendocine Differentiation, AR = Androgen Receptor and MDR = Multi Drug Resistance.