siRNA-based approaches for castration-resistant prostate cancer therapy targeting the androgen receptor signaling pathway

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Wang L, Lu B, He M, Wang Y, Wang Z, Du L. Prostate cancer incidence and mortality: global status and temporal trends in 89 countries from 2000 to 2019. Front. Public Health 10, 811044 (2022).
  MedlineGoogle Scholar
• 2. Sung H, Ferlay J, Siegel RL et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71(3), 209–249 (2021).
  MedlineGoogle Scholar
• 3. Culp MB, Soerjomataram I, Efstathiou JA, Bray F, Jemal A. Recent global patterns in prostate cancer incidence and mortality rates. Eur. Urol. 77(1), 38–52 (2019).
  MedlineGoogle Scholar
• 4. Aurilio G, Cimadamore A, Mazzucchelli R et al. Androgen receptor signaling pathway in prostate cancer: from genetics to clinical applications. Cells 9(2653), 1–14 (2020).
  Google Scholar
• 5. Kamoto T. Evaluation and diagnosis for castration resistant prostate cancer: CRPC. Nihon Rinsho 72(12), 2103–2107 (2014).
  MedlineGoogle Scholar
• 6. Scher HI, Halabi S, Tannock I et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J. Clin. Oncol. 26(7), 1148–1159 (2008).
  MedlineGoogle Scholar
• 7. Morote J, Aguilar A, Planas J. Definition of castrate resistant prostate cancer: new insights. Biomedicines 10, 689 (2022).
  Medline CASGoogle Scholar
• 8. Shan X, Lu D, Chen Y. Efficacy and safety of androgen-deprivation therapy combined with docetaxel plus prednisone in high-burden metastatic hormone-sensitive prostate cancer. Cancer Manag. Res. 12, 4369–4377 (2020).
  MedlineGoogle Scholar
• 9. Pernigoni N, Zagato E, Calcinotto A et al. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. J. Urol. 208(1), 205–206 (2022).
  MedlineGoogle Scholar
• 10. Kong P, Zhang L, Zhang Z et al. Emerging proteins in CRPC: functional roles and clinical implications. Front. Oncol. 12, 873876 (2022).
  Medline CASGoogle Scholar
• 11. Huang J, Lin B, Li B, Cuvillier O. Anti-androgen receptor therapies in prostate cancer: a brief update and perspective. Front. Oncol. 12, 865350 (2022).
  Medline CASGoogle Scholar
• 12. Lokeshwar SD, Klaassen Z, Saad F. Treatment and trials in non-metastatic castration-resistant prostate cancer. Nat. Rev. Urol. 18(7), 433–442 (2021).
  MedlineGoogle Scholar
• 13. Kristen AV, Ajroud-Driss S, Conceição I, Gorevic P, Kyriakides T, Obici L. Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis. Neurodegener. Dis. Manag. 9(1), 5–23 (2019).
  Google Scholar
• 14. Scott LJ. Givosiran: first approval. Drugs 80(3), 335–339 (2020).
  MedlineGoogle Scholar
• 15. Scott LJ, Keam SJ. Lumasiran: first approval. Drugs 81(2), 277–282 (2021).
  Medline CASGoogle Scholar
• 16. Padda IS, Mahtani AU, Parmar M. Small Interfering RNA (siRNA) Based Therapy. StatPearls Publishing, Treasure Island (FL) (2023).
  Google Scholar
• 17. Ray KK, Wright RS, Kallend D et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N. Engl. J. Med. 382(16), 1507–1519 (2020).
  Medline CASGoogle Scholar
• 18. Mullard A. 2022 FDA approvals. Nat. Rev. Drug Discov. 22(2), 83–88 (2023).
  Medline CASGoogle Scholar
• 19. Mullard A. FDA approves fifth RNAi drug – Alnylam’s next-gen hATTR treatment. Nat. Rev. Drug Discov. 21(8), 548–549 (2022).
  Google Scholar
• 20. Yamamoto Y, Lin PJC, Beraldi E et al. siRNA lipid nanoparticle potently silences clusterin and delays progression when combined with androgen receptor cotargeting in enzalutamide-resistant prostate cancer. Clin. Cancer Res. 21(21), 4845–4855 (2015).
  Medline CASGoogle Scholar
• 21. Albala DM. Imaging and treatment recommendations in patients with castrate-resistant prostate cancer. Rev. Urol. 19(3), 200–202 (2017).
  MedlineGoogle Scholar
• 22. Vellky JE, Ricke WA. Development and prevalence of castration-resistant prostate cancer subtypes. Neoplasia. 22(11), 566–575 (2020).
  Medline CASGoogle Scholar
• 23. Massengill JC, Sun L, Moul JW et al. Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. J. Urol. 169(5), 1670–1675 (2003).
  MedlineGoogle Scholar
• 24. Schatzl G, Madersbacher S, Thurridl T et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate 47(1), 52–58 (2001).
  Medline CASGoogle Scholar
• 25. Intasqui P, Bertolla RP, Sadi MV. Prostate cancer proteomics: clinically useful protein biomarkers and future perspectives. Expert Rev. Proteomics 15(1), 65–79 (2018).
  Medline CASGoogle Scholar
• 26. Liu X, Papukashvili D, Wang Z et al. Potential utility of miRNAs for liquid biopsy in breast cancer. Front. Oncol. 12, 940314 (2022).
  Medline CASGoogle Scholar
• 27. Iglesias-Gato D, Wikström P, Tyanova S et al. The proteome of primary prostate cancer. Eur. Urol. 69(5), 942–952 (2016).
  Medline CASGoogle Scholar
• 28. Trujillo B, Wu A, Wetterskog D, Attard G. Blood-based liquid biopsies for prostate cancer: clinical opportunities and challenges. Br. J. Cancer 127(8), 1394–1402 (2022).
  Medline CASGoogle Scholar
• 29. PDQ Adult Treatment Editorial Board. Prostate Cancer Treatment (PDQ®): Patient Version. National Cancer Institute, Bethesda, MD (2023).
  Google Scholar
• 30. Morgan SC, Hoffman K, Loblaw DA et al. Hypofractionated radiation therapy for localized prostate cancer: executive summary of an ASTRO, ASCO and AUA evidence-based guideline. J. Urol. 201(3), 528–534 (2019).
  MedlineGoogle Scholar
• 31. Posdzich P, Darr C, Hilser T et al. Metastatic prostate cancer – a review of current treatment options and promising new approaches. Cancers (Basel) 15(2), 461 (2023).
  Medline CASGoogle Scholar
• 32. Papukashvili D, Rcheulishvili N, Liu C et al. Perspectives on miRNAs targeting DKK1 for developing hair regeneration therapy. Cells 10(11), 2957 (2021).
  Medline CASGoogle Scholar
• 33. Daniels DL, Weis WI. β-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nat. Struct. Mol. Biol. 12(4), 364–371 (2005).
  Medline CASGoogle Scholar
• 34. Mehta S, Hingole S, Chaudhary V. The emerging mechanisms of Wnt secretion and signaling in development. Front. Cell Dev. Biol. 9, 714746 (2021).
  MedlineGoogle Scholar
• 35. Kimelman D, Xu W. β-Catenin destruction complex: insights and questions from a structural perspective. Oncogene 25(57), 7482–7491 (2006).
  Medline CASGoogle Scholar
• 36. Zhang Y, Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer. J. Hematol. Oncol. 13, 165 (2020).
  MedlineGoogle Scholar
• 37. Kypta RM, Waxman J. Wnt/β 2-catenin signalling in prostate cancer. Nat. Rev. Urol. 9(8), 418–428 (2012).
  Medline CASGoogle Scholar
• 38. Murillo-Garzón V, Kypta R. Wnt signalling in prostate cancer. Nat. Rev. Urol. 14(11), 683–69 (2017).
  Medline CASGoogle Scholar
• 39. Domingo-Domenech J, Mellado B, Ferrer B et al. Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse. Br. J. Cancer 93(11), 1285–1294 (2005).
  Medline CASGoogle Scholar
• 40. Staal J, Beyaert R. Inflammation and NF-κB signaling in prostate cancer: mechanisms and clinical implications. Cells 7(9), 122 (2018).
  Medline CASGoogle Scholar
• 41. Jin R, Yamashita H, Yu X et al. Inhibition of NF-kappa B signaling restores responsiveness of castrate resistant prostate cancer cells to anti-androgen treatment by decreasing androgen receptor variants expression. Oncogene 34(28), 3700–3710 (2015).
  Medline CASGoogle Scholar
• 42. He Y, Xu W, Xiao YT, Huang H, Gu D, Ren S. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials. Signal Transduct. Target. Ther. 7(1), 198 (2022).
  Medline CASGoogle Scholar
• 43. Hoang DT, Iczkowski KA, Kilari D, See W, Nevalainen MT. Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: opportunities for therapeutic targeting from multiple angles. Oncotarget 8(2), 3724–3745 (2017).
  MedlineGoogle Scholar
• 44. Ramalingam S, Ramamurthy VP, Njar VCO. Dissecting major signaling pathways in prostate cancer development and progression: mechanisms and novel therapeutic targets. J. Steroid Biochem. Mol. Biol. 166, 16–27 (2017).
  Medline CASGoogle Scholar
• 45. Shorning BY, Dass MS, Smalley MJ, Pearson HB. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling. Int. J. Mol. Sci. 21(12), 4507 (2020).
  Medline CASGoogle Scholar
• 46. Molina JR, Adjei AA. The Ras/Raf/MAPK pathway. J. Thorac. Oncol. 1(1), 7–9 (2006).
  MedlineGoogle Scholar
• 47. Schweizer MT, Yu EY. Persistent androgen receptor addiction in castration-resistant prostate cancer. J. Hematol. Oncol. 8(1), 128 (2015).
  MedlineGoogle Scholar
• 48. El-amm J, Aragon-ching JB. The current landscape of treatment in non-metastatic castration-resistant prostate cancer. Clin. Med. Insights Oncol. 13, 1179554919833927 (2019).
  Google Scholar
• 49. Hamid ARAH, Luna-Velez MV, Dudek AM, Schaafsma E, Sedelaar JPM, Schalken JA. Molecular phenotyping of AR signaling for predicting targeted therapy in castration resistant prostate cancer patient and tissue selection. Front. Oncol. 11, 721659 (2021).
  Medline CASGoogle Scholar
• 50. Chang C, Lee SO, Wang RS, Yeh S, Chang TM. Androgen receptor (AR) physiological roles in male and female reproductive systems: lessons learned from AR-knockout mice lacking AR in selective cells. Biol. Reprod. 89(1), 21 (2013).
  MedlineGoogle Scholar
• 51. Fujita K, Nonomura N. Role of androgen receptor in prostate cancer: a review. World J. Mens Health. 37(3), 288–295 (2019).
  MedlineGoogle Scholar
• 52. Eder IE, Culig Z, Putz T, Nessler-Menardi C, Bartsch G, Klocker H. Molecular biology of the androgen receptor: from molecular understanding to the clinic. Eur. Urol. 40(3), 241–251 (2001).
  Medline CASGoogle Scholar
• 53. Tan ME, Li J, Xu HE, Melcher K, Yong EL. Androgen receptor: structure, role in prostate cancer and drug discovery. Acta Pharmacol. Sin. 36(1), 3–23 (2015).
  Medline CASGoogle Scholar
• 54. Schalken J, Fitzpatrick JM. Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer. BJU Int. 117(2), 215–225 (2016).
  Medline CASGoogle Scholar
• 55. Robinson JLL, Hickey TE, Warren AY et al. Elevated levels of FOXA1 facilitate androgen receptor chromatin binding resulting in a CRPC-like phenotype. Oncogene 33(50), 5666–5674 (2014).
  Medline CASGoogle Scholar
• 56. Coutinho I, Day TK, Tilley WD, Selth LA. Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence. Endocr. Relat. Cancer. 23(12), T179–T197 (2016).
  Medline CASGoogle Scholar
• 57. Grasso CS, Wu Y, Robinson DR et al. The mutational landscape of lethal castrate resistant prostate cancer. Nature 487(7406), 239–243 (2013).
  Google Scholar
• 58. Podolak J, Eilers K, Newby T et al. Androgen receptor amplification is concordant between circulating tumor cells and biopsies from men undergoing treatment for metastatic castration resistant prostate cancer. Oncotarget 8(42), 71447–71455 (2017).
  MedlineGoogle Scholar
• 59. Azad AA, Volik SV, Wyatt AW et al. Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer. Clin. Cancer Res. 21(10), 2315–2324 (2015).
  Medline CASGoogle Scholar
• 60. Jiang Y, Palma JF, Agus DB, Wang Y, Gross ME. Detection of androgen receptor mutations in circulating tumor cells in castration-resistant prostate cancer. Clin. Chem. 56(9), 1492–1495 (2010).
  MedlineGoogle Scholar
• 61. Kwack MH, Sung YK, Chung EJ et al. Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. J. Invest. Dermatol. 128(2), 262–269 (2008).
  Medline CASGoogle Scholar
• 62. Premanand A, Rajkumari BR. Androgen modulation of Wnt/β-catenin signaling in androgenetic alopecia. Arch. Dermatol. Res. 310, 391–399 (2018).
  Medline CASGoogle Scholar
• 63. Yassa M, Saliou M, de rycke Y et al. Male pattern baldness and the risk of prostate cancer. Ann. Oncol. 22(8), 1824–1827 (2011).
  Medline CASGoogle Scholar
• 64. Muller DC, Giles GG, Sinclair R, Hopper JL, English DR, Severi G. Age-dependent associations between androgenetic alopecia and prostate cancer risk. Cancer Epidemiol. Biomarkers Prev. 22(2), 209–215 (2013).
  MedlineGoogle Scholar
• 65. He H, Xie B, Xie L. Male pattern baldness and incidence of prostate cancer: a systematic review and meta-analysis. Medicine 97(28), e11379 (2017).
  Google Scholar
• 66. Wright JL, Page ST, Lin DW, Stanford JL. Male pattern baldness and prostate cancer risk in a population-based case-control study. Cancer Epidemiol. 34(2), 131–135 (2010).
  MedlineGoogle Scholar
• 67. Khan S, Caldwell J, Wilson KM, Gonzalez-feliciano AG, Gerke TA, Markt SC. Baldness and risk of prostate cancer in the Health Professionals Follow-Up Study. Cancer Epidemiol. Biomarkers Prev. 29(6), 1229–1236 (2020).
  Medline CASGoogle Scholar
• 68. Flores-Morales A, Bergmann TB, Lavallee C et al. Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer. Clin. Cancer Res. 15(2), 595–608 (2019).
  Google Scholar
• 69. Parsons JK, Carter HB, Platz EA, Wright EJ, Landis P, Metter EJ. Serum testosterone and the risk of prostate cancer: potential implications for testosterone therapy. Cancer Epidemiol. Biomarkers Prev. 14(9), 2257–2260 (2005).
  Medline CASGoogle Scholar
• 70. Pierorazio PM, Ferrucci L, Kettermann A, Longo DL, Metter EJ, Carter HB. Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging. BJU Int. 105(6), 824–829 (2010).
  Medline CASGoogle Scholar
• 71. Stattin P, Lumme S, Tenkanen L et al. High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study. Int. J. Cancer 108(3), 418–424 (2004).
  Medline CASGoogle Scholar
• 72. Gui B, Gui F, Takai T et al. Selective targeting of PARP-2 inhibits androgen receptor signaling and prostate cancer growth through disruption of FOXA1 function. Proc. Natl Acad. Sci. USA 116(29), 14573–14582 (2019).
  Medline CASGoogle Scholar
• 73. Tatarov O, Mitchell TJ, Seywright M, Leung HY, Brunton VG, Edwards J. Src family kinase activity is up-regulated in hormone-refractory prostate cancer. Clin. Cancer Res. 15(10), 3540–3549 (2009).
  Medline CASGoogle Scholar
• 74. Peacock JW, Takeuchi A, Hayashi N et al. SEMA 3C drives cancer growth by transactivating multiple receptor tyrosine kinases via plexin B1. EMBO Mol. Med. 10(2), 219–238 (2018).
  Medline CASGoogle Scholar
• 75. Lee CCW, Munuganti RSN, Peacock JW et al. Targeting semaphorin 3C in prostate cancer with small molecules. J. Endocr. Soc. 2(12), 1381–1394 (2018).
  Medline CASGoogle Scholar
• 76. Xu K, Shimelis H, Linn DE et al. Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination. Cancer Cell 15(4), 270–282 (2009).
  Medline CASGoogle Scholar
• 77. Welti J, Rodrigues DN, Sharp A et al. Analytical validation and clinical qualification of a new immunohistochemical assay for androgen receptor splice variant-7 protein expression in metastatic castration-resistant prostate cancer. Eur. Urol. 70(4), 599–608 (2016). • Findings underline the contribution of the AR splice variant AR-V7 to castration-resistant prostate cancer (CRPC) proliferation by activating both common AR/AR-V7 target and specific AR-V7 target.
  Medline CASGoogle Scholar
• 78. Sugiura M, Sato H, Okabe A et al. Identification of AR-V7 downstream genes commonly targeted by AR/AR-V7 and specifically targeted by AR-V7 in castration resistant prostate cancer. Transl. Oncol. 14(1), 100915 (2021).
  Medline CASGoogle Scholar
• 79. Xu D, Zhan Y, Qi Y et al. Androgen receptor splice variants dimerize to transactivate target genes. Cancer Res. 75(17), 3663–3671 (2015).
  Medline CASGoogle Scholar
• 80. Stuopelyte K, Sabaliauskaite R, Bakavicius A et al. Analysis of AR-FL and AR-V1 in whole blood of patients with castration resistant prostate cancer as a tool for predicting response to abiraterone acetate. J. Urol. 204(1), 71–78 (2020).
  MedlineGoogle Scholar
• 81. Li Q, Wang Z, Yi J et al. Clinicopathological characteristics of androgen receptor splicing variant 7 (AR-V7) expression in patients with castration resistant prostate cancer: a systematic review and meta-analysis. Transl. Oncol. 14(9), 101145 (2021).
  Medline CASGoogle Scholar
• 82. Sharp A, Coleman I, Yuan W et al. Androgen receptor splice variant-7 expression emerges with castration resistance in prostate cancer. J. Clin. Invest. 129(1), 192–208 (2019).
  MedlineGoogle Scholar
• 83. Kanayama M, Lu C, Luo J, Antonarakis ES. AR splicing variants and resistance to AR targeting agents. Cancers (Basel) 13(11), 2563 (2021).
  Medline CASGoogle Scholar
• 84. Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr. Rev. 23(2), 175–200 (2002).
  Medline CASGoogle Scholar
• 85. Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat. Rev. Cancer 15(12), 701–711 (2015).
  Medline CASGoogle Scholar
• 86. Hu R, Dunn TA, Wei S et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone refractory prostate cancer. Cancer Res. 69(1), 16–22 (2009).
  Medline CASGoogle Scholar
• 87. Jiang N, Hjorth-Jensen K, Hekmat O et al. In vivo quantitative phosphoproteomic profiling identifies novel regulators of castration-resistant prostate cancer growth. Oncogene 34(21), 2764–2776 (2015).
  Medline CASGoogle Scholar
• 88. Lee HC, Ou CH, Huang YC et al. YAP1 overexpression contributes to the development of enzalutamide resistance by induction of cancer stemness and lipid metabolism in prostate cancer. Oncogene 40(13), 2407–2421 (2021).
  Medline CASGoogle Scholar
• 89. Ishizuya Y, Uemura M, Narumi R et al. The role of actinin-4 (ACTN4) in exosomes as a potential novel therapeutic target in castration-resistant prostate cancer. Biochem. Biophys. Res. Commun. 523(3), 588–594 (2020).
  Medline CASGoogle Scholar
• 90. Park S, Kang M, Kim S, An H, Gettemans J, Ko J. α-Actinin-4 promotes the progression of prostate cancer through the Akt/GSK-3β/β-catenin signaling pathway. Front. Cell Dev. Biol. 8, 588544 (2020).
  MedlineGoogle Scholar
• 91. Ingersoll MA, Chou YW, Lin JS et al. p66Shc regulates migration of castration-resistant prostate cancer cells. Cell. Signal. 46, 1–14 (2018).
  Medline CASGoogle Scholar
• 92. Miller DR, Ingersoll MA, Chatterjee A et al. p66Shc protein through a redox mechanism enhances the progression of prostate cancer cells towards castration-resistance. Free Radic. Biol. Med. 139, 24–34 (2019).
  Medline CASGoogle Scholar
• 93. Ai J, Jin T, Yang L et al. Vinculin and filamin-C are two potential prognostic biomarkers and therapeutic targets for prostate cancer cell migration. Oncotarget 8(47), 82430–82436 (2017).
  MedlineGoogle Scholar
• 94. Ai J, Lu Y, Wei Q, Li H. Comparative proteomics uncovers correlated signaling network and potential biomarkers for progression of prostate cancer. Cell. Physiol. Biochem. 41(1), 1–9 (2017).
  Medline CASGoogle Scholar
• 95. Bahmad HF, Peng W, Zhu R et al. Protein expression analysis of an in vitro murine model of prostate cancer progression: towards identification of high-potential therapeutic targets. J. Pers. Med. 10(3), 83 (2020).
  MedlineGoogle Scholar
• 96. Ni J, Cozzi P, Hao J et al. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway. Int. J. Biochem. Cell Biol. 45(12), 2736–2748 (2013).
  Medline CASGoogle Scholar
• 97. Saraon P, Cretu D, Musrap N et al. Quantitative proteomics reveals that enzymes of the ketogenic pathway are associated with prostate cancer progression. Mol. Cell. Proteomics 12(6), 1589–1601 (2013).
  Medline CASGoogle Scholar
• 98. Labanca E, Bizzotto J, Sanchis P et al. Prostate cancer castrate resistant progression usage of non-canonical androgen receptor signaling and ketone body fuel. Oncogene 40, 6284–6298 (2021).
  Medline CASGoogle Scholar
• 99. Höti N, Yang S, Hu Y, Shah P, Haffner MC, Zhang H. Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells. Prostate Cancer Prostatic Dis. 21(1), 137–146 (2018).
  Medline CASGoogle Scholar
• 100. Wang X, Chen J, Li QK et al. Overexpression of α(1,6) fucosyltransferase associated with aggressive prostate cancer. Glycobiology 24(10), 935–944 (2014).
  Medline CASGoogle Scholar
• 101. Höti N, Shah P, Hu Y, Yang S, Zhang H. Proteomics analyses of prostate cancer cells reveal cellular pathways associated with androgen resistance. Proteomics. 17(6), 10.1002/pmic.201600228 (2017).
  Google Scholar
• 102. Ferrari N, Granata I, Capaia M et al. Adaptive phenotype drives resistance to androgen deprivation therapy in prostate cancer. Cell Commun. Signal. 15(1), 51 (2017).
  MedlineGoogle Scholar
• 103. Barboro P, Benelli R, Tosetti F et al. Aspartate β-hydroxylase targeting in castration-resistant prostate cancer modulates the NOTCH/HIF1α/GSK3β crosstalk. Carcinogenesis 41(9), 1246–1252 (2020).
  Medline CASGoogle Scholar
• 104. Blomme A, Ford CA, Mui E et al. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nat. Commun. 11(1), 2508 (2020).
  Medline CASGoogle Scholar
• 105. Gong Y, Chippada-venkata UD, Galsky MD, Huang J, Oh WK. Elevated circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) levels are associated with neuroendocrine differentiation in castration resistant prostate cancer. Prostate 75(6), 616–627 (2015).
  Medline CASGoogle Scholar
• 106. Wise GJ, Marella VK, Talluri G, Shirazian D. Cytokine variations in patients with hormone treated prostate cancer. J. Urol. 164(3 I), 722–725 (2000).
  Medline CASGoogle Scholar
• 107. Izumi K, Fang LY, Mizokami A et al. Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2-induced STAT3 activation. EMBO Mol. Med. 5(9), 1383–1401 (2013).
  Medline CASGoogle Scholar
• 108. Papukashvili D, Liu C, Rcheulishvili N et al. DKK1-targeting cholesterol-modified siRNA implication in hair growth regulation. Biochem. Biophys. Res. Commun. 668, 55–61 (2023).
  Medline CASGoogle Scholar
• 109. Zhao J, Lin H, Wang L, Guo K, Jing R, Li X. Suppression of FGF5 and FGF18 expression by cholesterol-modified siRNAs promotes hair growth in mice. Front. Pharmacol. 12, 666860 (2021).
  Medline CASGoogle Scholar
• 110. Alshaer W, Zureigat H, Al A et al. siRNA: mechanism of action, challenges, and therapeutic approaches. Eur. J. Pharmacol. 905, 174178 (2021).
  Medline CASGoogle Scholar
• 111. Subhan MA, Attia SA, Torchilin VP. Advances in siRNA delivery strategies for the treatment of MDR cancer. Life Sci. 274, 119337 (2021).
  Medline CASGoogle Scholar
• 112. Zhang MM, Bahal R, Rasmussen TP, Manautou JE, Zhong X-B. The growth of siRNA-based therapeutics: updated clinical studies. Biochem. Pharmacol. 189, 114432 (2021).
  Medline CASGoogle Scholar
• 113. Lam JKW, Chow MYT, Zhang Y, Leung SWS. siRNA versus miRNA as therapeutics for gene silencing. Mol. Ther. Nucleic Acids 4(9), e252 (2015).
  Medline CASGoogle Scholar
• 114. Ahn I, Kang C, Han J. Where should siRNAs go: applicable organs for siRNA drugs. Exp. Mol. Med. 55(7), 1283–1292 (2023).
  Medline CASGoogle Scholar
• 115. Jing X, Arya V, Reynolds KS, Rogers H. Clinical pharmacology of RNA interference–based therapeutics: a summary based on Food and Drug Administration-approved small interfering RNAs. Drug Metab. Dispos. 51(2), 193–198 (2023).
  Medline CASGoogle Scholar
• 116. Hariharan VN, Shin M, Chang C-W et al. Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection. Proc. Natl Acad. Sci. USA 120(11), 2017 (2017).
  Google Scholar
• 117. Kim H, Mun D, Kang JY, Lee SH, Yun N, Joung B. Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis. Mol. Ther. Nucleic Acids 24, 1024–1032 (2021).
  Medline CASGoogle Scholar
• 118. Tang W, Chen Y, Jang HS et al. Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury. J. Control. Release 341, 300–313 (2022).
  Medline CASGoogle Scholar
• 119. Khan T, Weber H, Dimuzio J et al. Silencing myostatin using cholesterol-conjugated siRNAs induces muscle growth. Mol. Ther. Nucleic Acids 5(8), e342 (2016).
  Medline CASGoogle Scholar
• 120. Yan H, Hu Y, Akk A, Wickline SA, Pan H, Pham CTN. Peptide-siRNA nanoparticles targeting NF-κB p50 mitigate experimental abdominal aortic aneurysm progression and rupture. Biomater. Adv. 139, 213009 (2022).
  Medline CASGoogle Scholar
• 121. Nanna AR, Kel'in AV, Theile C et al. Generation and validation of structurally defined antibody–siRNA conjugates. Nucleic Acids Res. 48(10), 5281–5293 (2020).
  Medline CASGoogle Scholar
• 122. Zhang Y, Duan H, Zhao H et al. Development and evaluation of a PSMA-targeted nanosystem co-packaging docetaxel and androgen receptor siRNA for castration-resistant prostate cancer treatment. Pharmaceutics 14(5), 964 (2022).
  Medline CASGoogle Scholar
• 123. 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. 23(1), 163–172 (2022).
  Medline CASGoogle Scholar
• 124. Chen J, Yang Y, Xu D et al. Mesoporous silica nanoparticles combined with AKR1C3 siRNA inhibited the growth of castration-resistant prostate cancer by suppressing androgen synthesis in vitro and in vivo. Biochem. Biophys. Res. Commun. 540, 83–89 (2021). • Findings indicate the potential efficacy of inactivating AR signals by MSNs-siAKR1C3 for the treatment of CRPC.
  Medline CASGoogle Scholar
• 125. Compagno D, Merle C, Morin A et al. siRNA-directed in vivo silencing of androgen receptor inhibits the growth of castration-resistant prostate carcinomas. PLOS ONE 2(10), e1006 (2007).
  MedlineGoogle Scholar
• 126. Zhang X, He Z, Xiang L et al. Codelivery of GRP78 siRNA and docetaxel via RGD-PEG-DSPE/DOPA/CaP nanoparticles for the treatment of castration-resistant prostate cancer. Drug Des. Devel. Ther. 13, 1357–1372 (2019). • Findings indicate the potential efficacy of siRNA application for CRPC therapy and other cancers.
  Medline CASGoogle Scholar
• 127. Oner E, Kotmakci M, Baird AM et al. Development of EphA2 siRNA-loaded lipid nanoparticles and combination with a small-molecule histone demethylase inhibitor in prostate cancer cells and tumor spheroids. J. Nanobiotechnology 19, 71 (2021).
  Medline CASGoogle Scholar
• 128. Liao X, Tang S, Thrasher JB, Griebling TL, Li B. Small-interfering RNA-induced androgen receptor silencing leads to apoptotic cell death in prostate cancer. Mol. Cancer Ther. 4(4), 505–515 (2005). •• The study provides promising results of using siRNA for cell-targeted gene silencing in prostate cancer (PCa).
  Medline CASGoogle Scholar
• 129. Yang C, Ma D, Lu L, Yang X, Xi Z. Synthesis of KUE-siRNA conjugates for prostate cancer cell-targeted gene silencing. ChemBioChem 22(19), 2888–2895 (2021).
  Medline CASGoogle Scholar
• 130. Lee JB, Zhang K, Tam YYC et al. Lipid nanoparticle siRNA systems for silencing the androgen receptor in human prostate cancer in vivo. Int. J. Cancer 131(5), E781–790 (2012).
  Medline CASGoogle Scholar
• 131. Ashrafizadeh M, Hushmandi K, Moghadam ER et al. Progress in delivery of siRNA-based therapeutics employing nano-vehicles for treatment of prostate cancer. Bioengineering 7(3), 91 (2020).
  Medline CASGoogle Scholar
• 132. Hattab D, Gazzali AM, Bakhtiar A. Clinical advances of siRNA-based nanotherapeutics for cancer treatment. Pharmaceutics 13(7), 1009 (2021).
  Medline CASGoogle Scholar
• 133. Cheng H, Snoek R, Ghaidi F, Cox ME, Rennie PS. Short hairpin RNA knockdown of the androgen receptor attenuates ligand-independent activation and delays tumor progression. Cancer Res. 66(21), 10613–10620 (2006).
  Medline CASGoogle Scholar
• 134. Luna Velez MV, Verhaegh GW, Smit F, Sedelaar JPM, Schalken JA. Suppression of prostate tumor cell survival by antisense oligonucleotide-mediated inhibition of AR-V7 mRNA synthesis. Oncogene 38(19), 3696–3709 (2019).
  MedlineGoogle Scholar
• 135. Yang J, Xie SX, Huang Y et al. Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice. Nanomedicine 7(9), 1297–1309 (2012). •• Findings reveal that a form of ‘death induced by survival gene elimination’ mechanism in PCa cells which targets androgen receptor signaling may be a novel therapeutic strategy for PCa.
  CASGoogle Scholar
• 136. Corbin JM, Georgescu C, Wren JD, Xu C, Asch AS, Ruiz-Echevarría MJ. Seed-mediated RNA interference of androgen signaling and survival networks induces cell death in prostate cancer cells. Mol. Ther. Nucleic Acids 24, 337–351 (2021).
  Medline CASGoogle Scholar
• 137. Hååg P, Bektic J, Bartsch G, Klocker H, Eder IE. Androgen receptor down regulation by small interference RNA induces cell growth inhibition in androgen sensitive as well as in androgen independent prostate cancer cells. J. Steroid Biochem. Mol. Biol. 96(3–4), 251–258 (2005).
  Medline CASGoogle Scholar
• 138. Sun A, Tang J, Terranova PF, Zhang X, Thrasher JB, Li B. Adeno-associated virus-delivered short hairpin-structured RNA for androgen receptor gene silencing induces tumor eradication of prostate cancer xenografts in nude mice: a preclinical study. Int. J. Cancer 126(3), 764–774 (2010).
  Medline CASGoogle Scholar
• 139. Snoek R, Cheng H, Margiotti K et al. In vivo knockdown of the androgen receptor results in growth inhibition and regression of well-established, castration-resistant prostate tumors. Clin. Cancer Res. 15(1), 39–47 (2009).
  Medline CASGoogle Scholar
• 140. Walsh EE, Frenck RW, Falsey AR et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383(25), 2439–2450 (2020).
  Medline CASGoogle Scholar
• 141. Haas EJ, Angulo FJ, McLaughlin JM et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet 397(10287), 1819–1829 (2021).
  Medline CASGoogle Scholar
• 142. Corbett KS, Flynn B, Foulds KE et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med. 383(16), 1544–1555 (2020).
  Medline CASGoogle Scholar
• 143. Wang X, Liu C, Rcheulishvili N et al. Strong immune responses and protection of PcrV and OprF-I mRNA vaccine candidates against Pseudomonas aeruginosa. NPJ Vaccines 8(1), 76 (2023).
  Medline CASGoogle Scholar
• 144. Liu C, Rcheulishvili N, Shen Z et al. Development of an LNP-encapsulated mRNA-RBD vaccine against SARS-CoV-2 and its variants. Pharmaceutics 14(5), 1101 (2022).
  Medline CASGoogle Scholar
• 145. Papukashvili D, Rcheulishvili N, Liu C, Ji Y, He Y, Wang PG. Self-amplifying RNA approach for protein replacement therapy. Int. J. Mol. Sci. 23(21), 12884 (2022).
  Medline CASGoogle Scholar
• 146. Liu C, Papukashvili D, Dong Y et al. Identification of tumor antigens and design of mRNA vaccine for colorectal cancer based on the immune subtype. Front. Cell Dev. Biol. 9, 783527 (2022).
  MedlineGoogle Scholar
• 147. Chaudhary N, Weissman D, Whitehead KA. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat. Rev. Drug Discov. 20(11), 817–838 (2021).
  Medline CASGoogle Scholar
• 148. Lu ZJ, Mathews DH. OligoWalk: an online siRNA design tool utilizing hybridization thermodynamics. Nucleic Acids Res. 36(Web Server issue), 104–108 (2008).
  Google Scholar
• 149. Mahmoodi Chalbatani G, Dana H, Gharagouzloo E et al. Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach. Int. J. Nanomedicine 14, 3111–3128 (2019).
  MedlineGoogle Scholar
• 150. Wadosky KM, Koochekpour S. Androgen receptor splice variants and prostate cancer: from bench to bedside. Oncotarget 8(11), 18550–18576 (2017).
  MedlineGoogle Scholar
• 151. Zheng Z, Li J, Liu Y et al. The crucial role of AR-V7 in enzalutamide-resistance of castration-resistant prostate cancer. Cancers (Basel) 14(19), 4877 (2022).
  Medline CASGoogle Scholar
• 152. Zhao S, Liao J, Zhang S, Shen M, Li X, Zhou L. The positive relationship between androgen receptor splice variant-7 expression and the risk of castration-resistant prostate cancer: a cumulative analysis. Front. Oncol. 13, 1053111 (2023).
  Medline CASGoogle Scholar
• 153. Sobhani N, Neeli PK, D'Angelo A et al. AR-V7 in metastatic prostate cancer: a strategy beyond redemption. Int. J. Mol. Sci. 22, 5515 (2021).
  Medline CASGoogle Scholar
• 154. Liu X, Ledet E, Li D et al. A whole blood assay for AR-V7 and ARv567es in patients with prostate cancer. J. Urol. 196(6), 1758–1763 (2016).
  Medline CASGoogle Scholar
• 155. Bernemann C, Humberg V, Thielen B et al. Comparative analysis of AR variant AR-V567es mRNA detection systems reveals eminent variability and questions the role as a clinical biomarker in prostate cancer. Clin. Cancer Res. 25(13), 3856–3864 (2019).
  Medline CASGoogle Scholar
• 156. Kohli M, Ho Y, Hillman DW et al. Androgen receptor variant AR-V9 is coexpressed with AR-V7 in prostate cancer metastases and predicts abiraterone resistance. Clin. Cancer Res. 23(16), 4704–4715 (2017).
  Medline CASGoogle Scholar
• 157. Kallio HML, Hieta R, Latonen L et al. Constitutively active androgen receptor splice variants AR-V3, AR-V7 and AR-V9 are co-expressed in castration-resistant prostate cancer metastases. Br. J. Cancer 119(3), 347–356 (2018).
  Medline CASGoogle Scholar
• 158. Ledford H. Gene-silencing drug approved. Nature 560(7718), 291–292 (2018).
  Medline CASGoogle Scholar
• 159. Hoy SM. Patisiran: first global approval. Drugs 78(15), 1625–1631 (2018).
  Medline CASGoogle Scholar
• 160. Mullard A. RNAi agents score an approval and drive an acquisition. Nat. Rev. Drug Discov. 19(1), 10 (2020).
  Google Scholar
• 161. Mullard A. 2020 FDA drug approvals. Nat. Rev. Drug Discov. 20(2), 85–90 (2021).
  Medline CASGoogle Scholar
• 162. Mullard A. 2021 FDA approvals. Nat. Rev. Drug Discov. 21(2), 83–88 (2022).
  Medline CASGoogle Scholar