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Exosomes and prostate cancer management
Seminars in Cancer Biology ( IF 12.1 ) Pub Date : 2021-08-09 , DOI: 10.1016/j.semcancer.2021.08.004
V Vlaeminck-Guillem 1
Affiliation  

Exosomes (and other extracellular vesicles) are now part of the cancer research landscape, involved both as players in pathophysiological mechanisms, as biomarkers of the cancer process and as therapeutic tools. One step they have yet to take is to move into routine clinical practice and management of prostate cancer is an example of this necessary maturation. More than for many other cancers and because a possible alternative is active surveillance (neither removal nor destruction), the diagnosis of prostate cancer does not only involve the detection of cancerous cells but also the determination of its true aggressiveness. By measuring TRMPRSS2:ERG fusion and PCA3 transcripts in urine exosomes, the EPI assay seems able to help prostate biopsy decision. Results from clinical studies showed that it can reduce the proportion of unnecessary biopsies while missing only a minimal proportion of clinically significant cancers. In metastatic prostate cancer, after failure of a first step androgen deprivation therapy, when a choice has to be made between a second-generation androgen receptor (AR) signaling inhibitor and taxane-based chemotherapy, detection of the AR splicing variant AR-V7 in circulating tumor cells (CTCs) has appeared promising. Whether exosomes could be a better material (simpler to isolate from the bloodstream than CTCs?) to detect AR-V7 has been suggested by some studies and remains to be confirmed. At last, a couple of exploratory studies either targeted or used exosomes to treat prostate cancer, by respectively inhibiting their secretion (to prevent exosome-mediated transfer of biologically active oncogenic actors), or loading them with immunogenic cancer-specific proteins (to generate anticancer vaccine) or with pharmacologic agents. Overall efforts are however still needed to confirm these results and generalize exosome-based diagnostic, prognostic or therapeutic strategies in prostate cancer management.



中文翻译:

外泌体和前列腺癌管理

外泌体(和其他细胞外囊泡)现在是癌症研究领域的一部分,既作为病理生理机制的参与者,作为癌症过程的生物标志物,又作为治疗工具。他们尚未采取的一个步骤是进入常规临床实践,前列腺癌的管理就是这种必要成熟的一个例子。与许多其他癌症相比,由于一种可能的替代方法是主动监测(既不去除也不破坏),前列腺癌的诊断不仅涉及检测癌细胞,还涉及确定其真正的侵袭性。通过测量尿液外泌体中的 TRMPRSS2:ERG 融合和 PCA3 转录本,EPI 检测似乎能够帮助做出前列腺活检决策。临床研究的结果表明,它可以减少不必要的活检比例,同时只漏掉一小部分有临床意义的癌症。在转移性前列腺癌中,第一步雄激素剥夺疗法失败后,当必须在第二代雄激素受体 (AR) 信号抑制剂和基于紫杉烷的化疗之间做出选择时,检测 AR 剪接变体 AR-V7循环肿瘤细胞 (CTC) 似乎很有希望。外泌体是否是一种更好的材料(比 CTC 更容易从血流中分离出来?)来检测 AR-V7 是否已被一些研究提出并有待证实。最后,一些探索性研究针对或使用外泌体治疗前列腺癌,通过分别抑制它们的分泌(以防止外泌体介导的生物活性致癌因子的转移),或用免疫原性癌症特异性蛋白质(以产生抗癌疫苗)或药物来加载它们。然而,仍需要总体努力来确认这些结果,并在前列腺癌管理中推广基于外泌体的诊断、预后或治疗策略。

更新日期:2021-08-09
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