Abstract
Simple SummaryAdvanced prostate cancer remains currently an important cause of cancer death. Despite the emergence of new treatments during the last decade, their efficiency is limited due to therapeutic resistance of tumor cells. Extracellular vesicles are secreted by cells and play an important role in cell–cell communications. Their content is specific to the cell that produced them, and they can be isolated from biological fluids such as blood and urine. In this review, we highlight the recent results demonstrating the impact of extracellular vesicles in the mechanisms leading to therapeutic resistance and their use to find new predictive biomarkers in order to facilitate treatment decision and personalized medicine.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.
Highlights
In 2018, prostate cancer (PCa) incidence worldwide was estimated at 1.3 million new cases, associated with 359,000 deaths, ranking PCa as the second most frequent cancer and the fifth leading cause of cancer death among men [1].Therapeutic approaches and prognosis of PCa depend on its stage at diagnosis (Figure 1)
The androgen receptor (AR) axis plays a key role in the development of metastatic castrate-resistant prostate cancer (mCRPC)
A link between extracellular vesicles (EVs) and ADT resistance was proposed by Soekmadji et al EVs were isolated from androgen-dependent LNCaP cells that were deprived of androgen or treated with the AR inhibitor enzalutamide
Summary
In 2018, prostate cancer (PCa) incidence worldwide was estimated at 1.3 million new cases, associated with 359,000 deaths, ranking PCa as the second most frequent cancer and the fifth leading cause of cancer death among men [1]. 2015, therapy is used for ADT untreated essentially includes docetaxel taxane, thatthis inhibits microtubular depolymerization, in metastatic cancer, metastatic hormonal sensitiveisor hormonal naïve (mHSPC), combination with named. Astatic cancer, named metastatic hormonal sensitive or hormonal naïve cancer (mHSPC), Cabazitaxel,progression-free a second-generation semisynthetic is currently for Additiontreatment improving survival (PFS) and taxane, an overall survival restricted (OS) [3,4,9]. Cabazitaxel failedwith to show survival benefit in the first-line setting compared treatment of men with mCRPC a disease which has progressed during or after docetto docetaxel [11]. As therapeutic resistances occur in advanced PCa, the understanding of resistance mechanisms should allow one to identify new molecular targets and define new therapeutic strategies to thwart them In this context, extracellular vesicles (EVs) may appear as very promising tools. We highlight the roles of EVs in therapeutic resistance mechanisms in an advanced PCa context and their promising use to discover new predictive biomarkers
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