REFERENCES
2. Lepor H. Pathophysiology of benign prostatic hyperplasia in the aging male population. Rev Urol 2005;7:S3-12.
3. Platz EA, Joshu CE, Mondul AM, Peskoe SB, Willett WC, Giovannucci E. Incidence and progression of lower urinary tract symptoms in a large prospective cohort of United States men. J Urol 2012;188:496-501.
4. Lee KL, Peehl DM. Molecular and cellular pathogenesis of benign prostatic hyperplasia. J Urol 2004;172:1784-91.
5. Middleton LW, Shen Z, Varma S, et al. Genomic analysis of benign prostatic hyperplasia implicates cellular re-landscaping in disease pathogenesis. JCI Insight 2019;5:e129749.
6. American Cancer Society. Cancer facts & figures 2026. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2026/2026-cancer-facts-and-figures.pdf?utm_source=chatgpt.com. [Last accessed on 17 Apr 2026].
7. National Cancer Institute. SEER cancer stat facts: prostate cancer. Available from: https://seer.cancer.gov/statfacts/html/prost.html. [Last accessed on 17 Apr 2026].
8. Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res 2009;15:4792-8.
9. Shen MM, Abate-Shen C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev 2010;24:1967-2000.
10. Aggarwal R, Zhang T, Small EJ, Armstrong AJ. Neuroendocrine prostate cancer: subtypes, biology, and clinical outcomes. J Natl Compr Canc Netw 2014;12:719-26.
11. Aggarwal RR, Small EJ. Small-cell/neuroendocrine prostate cancer: a growing threat? Oncology (Williston Park) 2014;28:838-40.
12. de Kouchkovsky I, Chan E, Schloss C, Poehlein C, Aggarwal R. Diagnosis and management of neuroendocrine prostate cancer. Prostate 2024;84:426-40.
13. Saini S, Sreekumar A, Nathani S, Asante DM, Simmons MN. A novel exosome based therapeutic intervention against neuroendocrine prostate cancer. Sci Rep 2024;14:2816.
14. Aggarwal R, Huang J, Alumkal JJ, et al. Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: a multi-institutional prospective study. J Clin Oncol 2018;36:2492-503.
15. Asao T, Tobias GC, Lucotti S, Jones DR, Matei I, Lyden D. Extracellular vesicles and particles as mediators of long-range communication in cancer: connecting biological function to clinical applications. Extracell Vesicles Circ Nucl Acids 2023;4:461-85.
16. Doyle LM, Wang MZ. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells 2019;8:727.
17. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002;2:569-79.
18. Dey D, Ghosh S, Mirgh D, Panda SP, Jha NK, Jha SK. Role of exosomes in prostate cancer and male fertility. Drug Discov Today 2023;28:103791.
19. Skog J, Würdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008;10:1470-6.
20. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-9.
21. Taverna S, Pucci M, Alessandro R. Extracellular vesicles: small bricks for tissue repair/regeneration. Ann Transl Med 2017;5:83.
22. Minciacchi VR, Zijlstra A, Rubin MA, Di Vizio D. Extracellular vesicles for liquid biopsy in prostate cancer: where are we and where are we headed? Prostate Cancer Prostatic Dis 2017;20:251-8.
23. Di Vizio D, Morello M, Dudley AC, et al. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. Am J Pathol 2012;181:1573-84.
24. Vlaeminck-Guillem V. Extracellular vesicles in prostate cancer carcinogenesis, diagnosis, and management. Front Oncol 2018;8:222.
25. Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018;7:1535750.
26. Urabe F, Yamada Y, Yamamoto S, et al. Extracellular vesicles and prostate cancer management: a narrative review. Transl Androl Urol 2024;13:442-53.
27. Pan J, Ding M, Xu K, Yang C, Mao LJ. Exosomes in diagnosis and therapy of prostate cancer. Oncotarget 2017;8:97693-700.
28. Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell 2016;30:836-48.
29. Lin CJ, Yun EJ, Lo UG, et al. The paracrine induction of prostate cancer progression by caveolin-1. Cell Death Dis 2019;10:834.
30. Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014;371:1028-38.
31. Onstenk W, Sieuwerts AM, Kraan J, et al. Efficacy of cabazitaxel in castration-resistant prostate cancer is independent of the presence of AR-V7 in circulating tumor cells. Eur Urol 2015;68:939-45.
32. Takeuchi T, Okuno Y, Hattori-Kato M, Zaitsu M, Mikami K. Detection of AR-V7 mRNA in whole blood may not predict the effectiveness of novel endocrine drugs for castration-resistant prostate cancer. Res Rep Urol 2016;8:21-5.
33. El-Sayed IY, Daher A, Destouches D, et al. Extracellular vesicles released by mesenchymal-like prostate carcinoma cells modulate EMT state of recipient epithelial-like carcinoma cells through regulation of AR signaling. Cancer Lett 2017;410:100-11.
34. Gabriel K, Ingram A, Austin R, et al. Regulation of the tumor suppressor PTEN through exosomes: a diagnostic potential for prostate cancer. PLoS ONE 2013;8:e70047.
35. Dai J, Escara-Wilke J, Keller JM, et al. Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis. J Exp Med 2019;216:2883-99.
36. Gao Z, Pang B, Li J, Gao N, Fan T, Li Y. Emerging role of exosomes in liquid biopsy for monitoring prostate cancer invasion and metastasis. Front Cell Dev Biol 2021;9:679527.
37. Hashimoto K, Ochi H, Sunamura S, et al. Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A. Proc Natl Acad Sci U S A 2018;115:2204-9.
38. Zhang J, Chen W, Zhang C, et al. Prostate cancer cells secrete PD-1 in exosomes to enhance myeloid-derived suppressor cell activity and promote tumor immune evasion. Cancer Res 2025;85:3435-53.
39. Ju Y, Watson J, Wang JJ, et al. B7-H3-liquid biopsy for the characterization and monitoring of the dynamic biology of prostate cancer. Drug Resist Updat 2025;79:101207.
40. Beltran H, Prandi D, Mosquera JM, et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med 2016;22:298-305.
41. Beltran H, Rickman DS, Park K, et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov 2011;1:487-95.
42. Dardenne E, Beltran H, Benelli M, et al. N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell 2016;30:563-77.
43. Lotan TL, Gupta NS, Wang W, et al. ERG gene rearrangements are common in prostatic small cell carcinomas. Mod Pathol 2011;24:820-8.
44. Maina PK, Shao P, Liu Q, et al. c-MYC drives histone demethylase PHF8 during neuroendocrine differentiation and in castration-resistant prostate cancer. Oncotarget 2016;7:75585-602.
45. Deeble PD, Cox ME, Frierson HF Jr, et al. Androgen-independent growth and tumorigenesis of prostate cancer cells are enhanced by the presence of PKA-differentiated neuroendocrine cells. Cancer Res 2007;67:3663-72.
46. Lin LC, Gao AC, Lai CH, Hsieh JT, Lin H. Induction of neuroendocrine differentiation in castration resistant prostate cancer cells by adipocyte differentiation-related protein (ADRP) delivered by exosomes. Cancer Lett 2017;391:74-82.
47. Patel GK, Dutta S, Syed MM, et al. TBX2 drives neuroendocrine prostate cancer through exosome-mediated repression of miR-200c-3p. Cancers 2021;13:5020.
48. Verrillo CE, Quaglia F, Shields CD, et al. Expression of the αVβ3 integrin affects prostate cancer sEV cargo and density and promotes sEV pro-tumorigenic activity in vivo through a GPI-anchored receptor, NgR2. J Extracell Vesicles 2024;13:e12482.
49. Yeon M, Perego M, Elokely KM, et al. Parkin induces ubiquitination and large extracellular vesicle release of HMGB1 to activate antitumor immunity. Cancer Res 2025;85:5033-48.
50. Vives-Bauza C, Zhou C, Huang Y, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A 2010;107:378-83.
51. Bhagirath D, Yang TL, Tabatabai ZL, et al. BRN4 is a novel driver of neuroendocrine differentiation in castration-resistant prostate cancer and is selectively released in extracellular vesicles with BRN2. Clin Cancer Res 2019;25:6532-45.
52. Bishop JL, Thaper D, Vahid S, et al. The master neural transcription factor BRN2 is an androgen receptor-suppressed driver of neuroendocrine differentiation in prostate cancer. Cancer Discov 2017;7:54-71.
53. Peak TC, Panigrahi GK, Praharaj PP, et al. Syntaxin 6-mediated exosome secretion regulates enzalutamide resistance in prostate cancer. Mol Carcinog 2020;59:62-72.
55. Pang B, Zhu Y, Ni J, et al. Extracellular vesicles: the next generation of biomarkers for liquid biopsy-based prostate cancer diagnosis. Theranostics 2020;10:2309-26.
56. Logozzi M, Angelini DF, Giuliani A, et al. Increased plasmatic levels of PSA-expressing exosomes distinguish prostate cancer patients from benign prostatic hyperplasia: a prospective study. Cancers 2019;11:1449.
57. Logozzi M, Angelini DF, Iessi E, et al. Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients. Cancer Lett 2017;403:318-29.
58. Sandúa A, Sanmamed MF, Rodríguez M, et al. PSA reactivity in extracellular microvesicles to commercial immunoassays. Clin Chim Acta 2023;543:117303.
59. Moreno A, Sandúa A, Ferrer-Costa R, et al. The analytical impact of extracellular vesicles PSA on different commercial total PSA measurement methods. Biochem Med 2026;36:010703.
60. Margolis E, Brown G, Partin A, et al. Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies. Prostate Cancer Prostatic Dis 2022;25:296-301.
61. McKiernan J, Noerholm M, Tadigotla V, et al. A urine-based exosomal gene expression test stratifies risk of high-grade prostate cancer in men with prior negative prostate biopsy undergoing repeat biopsy. BMC Urol 2020;20:138.
62. Wang X, Zhang L, Cheng L, et al. Extracellular vesicle-derived biomarkers in prostate cancer care: opportunities and challenges. Cancer Lett 2024;601:217184.
63. Del Re M, Biasco E, Crucitta S, et al. The detection of androgen receptor splice variant 7 in plasma-derived exosomal RNA strongly predicts resistance to hormonal therapy in metastatic prostate cancer patients. Eur Urol 2017;71:680-7.
64. Woo HK, Park J, Ku JY, et al. Urine-based liquid biopsy: non-invasive and sensitive AR-V7 detection in urinary EVs from patients with prostate cancer. Lab Chip 2018;19:87-97.
65. Strati A, Zavridou M, Bournakis E, Mastoraki S, Lianidou E. Expression pattern of androgen receptors, AR-V7 and AR-567es, in circulating tumor cells and paired plasma-derived extracellular vesicles in metastatic castration resistant prostate cancer. Analyst 2019;144:6671-80.
66. Miceli RT, Chen TY, Nose Y, et al. Extracellular vesicles, RNA sequencing, and bioinformatic analyses: challenges, solutions, and recommendations. J Extracell Vesicles 2024;13:e70005.
67. Li Y, Pan D, Wang Z, et al. The diagnostic value of urinary exosomes in prostate cancer: a prospective multicenter study. BMC Urol 2025;25:246.
68. Park YH, Shin HW, Jung AR, et al. Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer. Sci Rep 2016;6:30386.
69. Øverbye A, Skotland T, Koehler CJ, et al. Identification of prostate cancer biomarkers in urinary exosomes. Oncotarget 2015;6:30357-76.
70. Sequeiros T, Rigau M, Chiva C, et al. Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer. Oncotarget. 2017;8:4960-76.
71. Bijnsdorp IV, Geldof AA, Lavaei M, Piersma SR, van Moorselaar RJ, Jimenez CR. Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients. J Extracell Vesicles. 2013;2:22097.
72. Huang X, Yuan T, Liang M, et al. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur Urol. 2015;67:33-41.
73. Guo T, Wang Y, Jia J, et al. The identification of plasma exosomal miR-423-3p as a potential predictive biomarker for prostate cancer castration-resistance development by plasma exosomal miRNA sequencing. Front Cell Dev Biol 2020;8:602493.
74. Bhagirath D, Liston M, Akoto T, et al. Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients. Sci Rep 2021;11:8279.
75. Abida W, Campbell D, Patnaik A, et al. Rucaparib for the treatment of metastatic castration-resistant prostate cancer associated with a DNA damage repair gene alteration: final results from the phase 2 TRITON2 study. Eur Urol 2023;84:321-30.
76. Bhagirath D, Yang TL, Bucay N, et al. microRNA-1246 is an exosomal biomarker for aggressive prostate cancer. Cancer Res 2018;78:1833-44.
77. Zhang M, Hu S, Liu L, et al. Engineered exosomes from different sources for cancer-targeted therapy. Signal Transduct Target Ther 2023;8:124.
78. Sreekumar A, Simmons MN, Lee TJ, Sharma A, Saini S. Therapeutic potential of pomegranate juice-derived nanovesicles in nude mouse benign prostatic hyperplasia (BPH) xenograft model. Sci Rep 2023;13:12427.
79. Diao Y, Wang G, Zhu B, et al. Loading of “cocktail siRNAs” into extracellular vesicles via TAT-DRBD peptide for the treatment of castration-resistant prostate cancer. Cancer Biol Ther 2022;23:163-72.
80. Alonso-Magdalena P, Brössner C, Reiner A, et al. A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia. Proc Natl Acad Sci U S A 2009;106:2859-63.
81. Broster SA, Kyprianou N. Epithelial-mesenchymal transition in prostatic disease. Future Oncol 2015;11:3197-206.
82. Hu S, Yu W, Lv TJ, Chang CS, Li X, Jin J. Evidence of TGF-β1 mediated epithelial-mesenchymal transition in immortalized benign prostatic hyperplasia cells. Mol Membr Biol 2014;31:103-10.
83. Liu D, Liu J, Li Y, et al. Upregulated bone morphogenetic protein 5 enhances proliferation and epithelial-mesenchymal transition process in benign prostatic hyperplasia via BMP/Smad signaling pathway. Prostate 2021;81:1435-49.
84. Saari H, Lázaro-Ibáñez E, Viitala T, Vuorimaa-Laukkanen E, Siljander P, Yliperttula M. Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells. J Control Release 2015;220:727-37.
85. Gao K, Xi W, Ni J, et al. Genetically modified extracellular vesicles loaded with activated gasdermin D potentially inhibit prostate-specific membrane antigen-positive prostate carcinoma growth and enhance immunotherapy. Biomaterials 2025;315:122894.
86. Fan Z, Wang Z, Zhang H, et al. Extracellular vesicles derived from mature dendritic cells loaded with cDC1-specific chemokine XCL1 combined with chemotherapy-induced ICD for the treatment of castration-resistant prostate cancer. Cancer Immunol Immunother 2025;74:242.
87. Lee JK, Bangayan NJ, Chai T, et al. Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer. Proc Natl Acad Sci U S A 2018;115:E4473-82.
88. Antes TJ, Middleton RC, Luther KM, et al. Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display. J Nanobiotechnol 2018;16:61.
